Patient-derived Determinants for Participation in Placebo-controlled Clinical Trials for Fibromyalgia Effect of Transcutaneous Electrical Nerve Stimulation on Pain, Function, and Quality of Life in Fibromyalgia: A Double-Blind Randomized Clinical Trial A diabetes outcome progression trial (ADOPT): an international multicenter study of the comparative efficacy of rosiglitazone, glyburide, and metformin in recently diagnosed type 2 diabetes. Magnitude of the placebo effect in randomized trials of antiepileptic agents Comparison of effects of gliclazide, metformin and pioglitazone monotherapies on glycemic control and cardiovascular risk factors in patients with newly diagnosed uncontrolled type 2 diabetes mellitus. Efficacy of vildagliptin versus sulfonylureas as add-on therapy to metformin: comparison of results from randomised controlled and observational studies Efficacy of 24-week monotherapy with acarbose, metformin, or placebo in dietary-treated NIDDM patients: the Essen-II Study. Women's experiences as members of attention control and experimental intervention groups in a randomized controlled trial. Statins and Fibrates for Diabetic Retinopathy: Protocol for a Systematic Review Durability of efficacy and long-term safety profile of glyburide/metformin tablets in patients with type 2 diabetes mellitus: an open-label extension study. A comparison of the effects of rosiglitazone and glyburide on cardiovascular function and glycemic control in patients with type 2 diabetes. Evaluation of a Behavioral Mobile Phone App Intervention for the Self-Management of Type 2 Diabetes: Randomized Controlled Trial Protocol Challenges and Recommendations for Placebo Controls in Randomized Trials in Physical and Rehabilitation Medicine: A Report of the International Placebo Symposium Working Group Effect of acute and chronic whole-body vibration exercise on serum insulin-like growth factor-1 levels in women with fibromyalgia. Do the Effects of Psychological Treatments on Improving Glycemic Control in Type 1 Diabetes Persist Over Time? A Long-Term Follow-Up of a Randomized Controlled Trial Randomized double-blind placebo-controlled trial of lithium in youths with severe mood dysregulation. Cardiovascular Outcomes in Type 2 Diabetes: A double-blind placebo-controlled study of bezafibrate: the St. Mary's, Ealing, Northwick Park Diabetes Cardiovascular Disease Prevention (SENDCAP) Study
Perspectives of patients with fibromyalgia influence their likelihood of participating in r and omized placebo-controlled trials and potentially clash with current , well-established methodology of r and omized controlled trial design . M and ates to use only acetaminophen for breakthrough pain and that require discontinuation of concomitant medications , especially in studies lacking an active comparator arm , could bias a trial cohort to thereby reduce the generalizability of study findings and conclusions . This study evaluates factors affecting willingness to participate in such clinical trials , including the impact of altruism , payment , study duration , forced discontinuation of specific medications , and subject demographics for patients seen by rheumatologists proficient and avidly interested in treating fibromyalgia Background Fibromyalgia is a common chronic pain condition that has a significant impact on quality of life and often leads to disability . To date , there have been few well-controlled trials assessing the utility of nonpharmacological treatment modalities such as transcutaneous electrical nerve stimulation ( TENS ) in the management of pain and improvement in function in individuals with fibromyalgia . Objectives The purpose of this study will be to complete a long-term , multicenter study to assess the effects of TENS in women with fibromyalgia . Design This will be a phase II r and omized , double-blind , placebo-controlled , multicenter clinical trial . Participants Three hundred forty-three participants with fibromyalgia will be recruited for this study . Intervention Participants will be r and omly assigned to 1 of 3 groups : the intervention ( TENS ) , placebo , or no treatment . After completing the r and omized period , all participants will receive the intervention for 1 month . The participants will be asked to use TENS at the highest tolerable level for at least 2 hours daily during physical activity . Measurements The primary outcome will be pain with movement , with secondary outcomes assessing functional abilities , patient-reported outcomes , and quantitative sensory testing . Limitations Because having participants refrain from their typical medications is not practical , their usage and any change in medication use will be recorded . Conclusions The results of this study will provide some of the first evidence from a large-scale , double-blind , placebo-controlled trial on the effectiveness of TENS on pain control and quality -of-life changes in patients with fibromyalgia OBJECTIVE Therapies with metformin , sulfonylureas , or insulin improve glycemic control in the short term but do not prevent progressive islet beta-cell failure or long-term deterioration in glycemia . Our goal was to evaluate , in patients recently diagnosed with type 2 diabetes ( <3 years ) , the long-term efficacy of monotherapy with rosiglitazone on glycemic control and on the progression of pathophysiological abnormalities associated with type 2 diabetes as compared with metformin or glyburide monotherapy . RESEARCH DESIGN AND METHODS A Diabetes Outcome Progression Trial ( ADOPT ) is a r and omized , double-blind , parallel-group study consisting of a screening visit , a 4-week placebo run-in , a 4-year treatment period , and an observational follow-up of approximately 3,600 drug-naïve patients with type 2 diabetes diagnosed within the previous 3 years . After run-in , patients will be r and omized to rosiglitazone , glyburide , or metformin titrated to the maximum effective daily doses ( 8 mg rosiglitazone , 15 mg glyburide , or 2 g metformin ) . The primary outcome is time to monotherapy failure , defined as the time following titration to the maximal effective or tolerated dose when fasting plasma glucose exceeds 180 mg/dl ( 10 mmol/l ) . Secondary outcomes include measures of islet beta-cell function , insulin sensitivity , dyslipidemia , changes in urinary albumin excretion , plasminogen activator inhibitor-1 antigen , fibrinogen , and C-reactive protein . Safety and tolerability will also be evaluated . Patient-reported outcomes and re source utilization data will be collected and analyzed . CONCLUSIONS ADOPT will provide data on the effect of mechanistically differing treatment options on metabolic control , beta-cell function , and markers of macrovascular disease risk in type 2 diabetes Placebo-controlled r and omized trials ideally produce unbiased estimates of the treatment effect after accounting for nonpharmacological effects ( regression to the mean , Hawthorne , and placebo effects ) . Recognizing that the magnitude of these effects may help underst and why investigators need to control for them , we sought to measure this magnitude . We review ed published meta-analyses of r and omized , placebo-controlled add-on trials of antiepileptic medications versus placebo , included in the Cochrane Library . In r and omized trials of antiepileptic agents for epilepsy , 9.3 - 16.6 % of patients in the placebo arm had a > 50 % reduction in seizure frequency . This effect represents 20 - 50 % of the effect observed with active agents . Because patients with epilepsy in the placebo arm of r and omized trials experience a large clinical benefit due to nonpharmacological effects , r and omized controlled trials are necessary to gauge the true magnitude of the treatment effect of new antiepileptic agents OBJECTIVE The objective of this study was to evaluate and compare the effects of gliclazide-modified release ( gliclazide-MR ) , metformine ( MET ) and pioglitazone ( PIO ) monotherapies on glycemic control and conventional/non-conventional cardiovascular risk factors in patients with newly diagnosed type 2 diabetes mellitus ( T2DM ) . MATERIAL AND METHODS A single center , r and omized , 52-wk comparator-controlled clinical study was carried out in patients with newly diagnosed uncontrolled T2DM . A total of 57 patients were r and omized into gliclazide-MR , metformin and pioglitazone groups . Drugs were administered for 12 months . Anthropometric measurements , fasting plasma glucose ( FPG ) , postpr and ial plasma glucose ( PPG ) , HbA1c , insulin , HOMA-IR , lipid parameters , the markers of coagulation/fibrinolysis , inflammation and endothelial dysfunction were measured at baseline and at months 3 , 6 , and 12 . RESULTS In the gliclazide-MR group , HC , FPG , HbA1c , insulin , HOMA-IR , TC , trigylcerides , Lp ( a ) , E-selectin and Hcy were significantly decreased after treatment compared to baseline . In the MET group , BMI , WC , FPG , PPG , HbA1c , ICAM-1 and Hcy significantly decreased after treatment compared to baseline . In PIO group , WC , HC , FPG , PPG , HbA1c , C-peptid , HOMA-IR , trigylcerides , vWF , IL-6 , ICAM-1 , E-selectin and Hcy significantly decreased after treatment compared to baseline , whereas , HDL-C increased . At the end of the month 12 , the decreases in insulin and HOMA-IR score were more pronounced with PIO compared to gliclazide . CONCLUSIONS Gliclazide-MR , MET and PIO monotherapies , were equally effective in proving glycemic control in patients with newly diagnosed , oral antidiabetic (OAD)-naive T2DM . But , improvements in conventional/non-conventional cardiovascular risk factors were more pronounced in patients on PIO therapy compared to gliclazide and MET therapies . Also , all of the 3 drugs represent effective and safe first-line pharmacological treatment options in these patients Aims /hypothesisR and omised control trials ( RCTs ) do not always reflect real-life outcomes for glucose-lowering drugs . In this work we compared RCT and real-life data on the efficacy of the dipeptidyl peptidase-IV ( DPP-4 ) inhibitor vildagliptin or sulfonylureas when added to metformin . Methods Data were pooled from five RCTs examining vildagliptin ( n = 2,788 ) and sulfonylureas ( glimepiride [ n = 1,259 ] or gliclazide [ n = 433 ] ) , added to metformin . For real-life conditions , data were extracted from an observational study examining vildagliptin ( n = 7,002 ) or sulfonylureas ( n = 3,702 ) , added to metformin monotherapy . Linear regression analyses were performed between the baseline HbA1c and the change in HbA1c ( Δ HbA1c ) after 24 weeks . Results Baseline HbA1c correlated to Δ HbA1c ( r2 = 0.36 , slope = −0.54 [ 95 % CI −0.55 , −0.53 ; p < 0.0001 ] ) for both treatments . With sulfonylureas , the slope of the correlation was steeper in the observational study than in RCTs ( interaction coefficient = −0.327 , p < 0.001 ) , whereas for vildagliptin , the slope was virtually identical in the observational study and the RCTs ( interaction coefficient = 0.024 , p = 0.175 ) . For any given baseline HbA1c , Δ HbA1c  with sulfonylureas was smaller in real life than in RCTs , whereas Δ HbA1c with vildagliptin was the same . Conclusions /interpretationsWhen comparing RCT to real-life data , the decrease in HbA1c from baseline with sulfonylurea treatment is smaller in real life than in RCTs , whereas the reduction with vildagliptin is essentially the same , suggesting that the full power of treatment is retained in real life for vildagliptin but not for sulfonylureas , possibly due to fear of hypoglycaemia PURPOSE To compare the therapeutic potential of acarbose , metformin , or placebo as first line treatment in patients with non-insulin-dependent diabetes mellitus ( NIDDM ) . PATIENTS AND METHODS Ninety-six patients with NIDDM ( 35 - 70 years of age , body mass index ( BMI ) < or = 35 kg/m2 , insufficiently treated with diet alone , glycated hemoglobin ( HbA1c ; 7 % to 11 % ) were r and omized into 3 groups and treated for 24 weeks with acarbose , 3 x 100 mg/day , or metformin , 2 x 850 mg/day , or placebo .  Efficacy , based on HbA1c ( primary efficacy criterion ) ,  fasting blood glucose ( BG ) and  insulin , 1 hour postpr and ial BG and insulin  ( after st and ard meal test ) , postpr and ial insulin increase , plasma lipid profile , and tolerability , based on subjective symptoms and laboratory values were determined every 6 weeks . Analysis of covariance was performed for endvalues with adjustment on baseline values . Ninety-four patients were valid for efficacy evaluation . RESULTS Both active drugs showed the same improvement of efficacy criteria compared with placebo . Baseline adjusted means at endpoint were as follows : BG , fasting and 1 hour postpr and ial , 9.2 mM and 10.9 mM with placebo , 7.6 mM and 8.7 mM with acarbose , and 7.8 mM and 9.0 mM with metformin ; HbA1c was 9.8 % with placebo , 8.5 % with acarbose , and 8.7 % with metformin . Comparisons : acarbose versus placebo and metformin versus placebo were statistically significant , but not acarbose versus metformin . No effect on fasting insulin could be observed . Relative postpr and ial insulin increase was 1.90 with placebo , 1.09 with acarbose , and 1.03 with metformin . Comparisons : acarbose versus placebo and metformin versus placebo were statistically significant , but not acarbose versus metformin . With respect to lipid profile , acarbose was superior to metformin .  Low-density lipoprotein (LDL)/high-density lipoprotein ( HDL ) cholesterol ratio increased by 14.4 % with placebo , was unchanged with metformin , but decreased by 26.7 % with acarbose . Comparisons : acarbose versus placebo and acarbose versus metformin were statistically significant , but not metformin versus placebo . Slight body weight changes were observed with acarbose ( -0.8 kg ) and metformin ( -0.5 kg ) , but not with placebo . Acarbose led to mild or moderate intestinal symptoms in 50 % of the patients within the first 4 weeks , but in only 13.8 % of the patients within the last 4 weeks . CONCLUSIONS Acarbose and metformin are effective drugs for the first line monotherapy of patients with NIDDM . With respect to plasma lipid profile , especially HDL cholesterol , LDL cholesterol and LDL/HDL cholesterol ratio  acarbose may be superior to metformin Attention control groups are often used in research testing the efficacy of psychosocial and behavioural interventions in order to control for placebo effects . The authors conducted a descriptive qualitative study to investigate how participants viewed their experiences in attention control and experimental intervention groups following a r and omized controlled trial for women with fibromyalgia syndrome . Moderately structured interviews were conducted with 18 women ( 12 from the experimental intervention group and 6 from the attention control group ) . Members of the control group reported some benefits but few behavioural changes as a result of participating in the RCT , and some participants expressed disappointment at not receiving the intervention . Perceptions of changes in attitudes towards fibromyalgia syndrome and behaviours reported by the intervention group appear to be consistent with the theory underlying the intervention . Possible placebo effects identified in both groups include negative and positive social interactions with other participants Background Diabetic retinopathy ( DR ) is a common microvascular complication of diabetes mellitus , and more than 75 % of patients who have had diabetes for more than 20 years will have some degree of DR . This disease is highly destructive to self-esteem and puts a high burden on public health and pension systems due to the effects that it has on people of working age . The current mainstay of treatment is laser photocoagulation , which causes impairment of vision and discomfort to patients . Thus , finding a systemic drug that could act on all microcirculation and prevent direct manipulation of the eyes would be highly desirable . Objective To assess the efficacy and safety of the drugs in the statin and /or fibrate groups for the prevention and treatment of DR . Methods In this systematic review , we will select r and omized controlled trials of fibrates or statins used for the treatment or prevention of DR . Our search strategy will include free text terms and controlled vocabulary ( eg , MeSH , Emtree ) for , “ diabetic retinopathy ” , “ statins ” , “ fibrates ” , “ hypolipidemic agents ” , and for drugs from both groups . Data bases that will be used include Medical Literature Analysis and Retrieval System/ PubMed , Embase , Cochrane Central Register of Controlled Trials , Latin American and Caribbean Center on Health Sciences Information , Clinical trials.gov , World Health Organization International Clinical Trials Registry Platform , and OpenGrey , and we will not have language or date limits . Two review authors will independently select eligible studies and assess the risk of bias using the Cochrane Collaboration ’s tool . We will report structured summaries of the included studies and , if possible , conduct meta-analyses . Results This is a protocol for a systematic review , therefore results are not available . We registered a short version of this protocol before progressing in the review and we are currently in the process of selecting the studies for inclusion . Conclusions Intensive glucose control and lowering blood pressure and lipids are mechanisms that protect macrocirculation in diabetic patients . Both macrovascular and microvascular events in diabetic patients appear to have a common pathway , starting with endothelial injury . Thus , prevention and treatment of microvascular events may benefit from the same interventions . In the review for which we have written this protocol , we will assess whether the use of lipid-lowering oral drugs of the statin and /or fibrate groups may prevent and /or retard progression of DR , with the added benefit of preserving visual acuity . Trial Registration PROSPERO BACKGROUND Intensive glycemic control substantially reduces the microvascular and macrovascular complications of type 2 diabetes mellitus , although less than half of patients with diabetes achieve the target glycosylated hemoglobin ( HbA1c ) value recommended by the American Diabetes Association . Because monotherapy with an oral agent does not address the multiple pathophysiologic defects of diabetes , use of combination therapy appears to be warranted . A previous 32-week , r and omized , double-blind , placebo-controlled trial found that treatment with glyburide/metformin tablets was associated with greater reductions in HbA1c values compared with glyburide monotherapy , metformin monotherapy , and placebo . OBJECTIVES This study evaluated the durability of efficacy and long-term safety profile of therapy with glyburide/metformin tablets over 52 weeks . METHODS Patients enrolled in this open-label extension study were drawn from 3 groups : those who completed the 32-week double-blind study , those who were discontinued from the double-blind study , and those who were ineligible for the double-blind study and were enrolled directly in the open-label extension study . Patients with an HbA1c of < 9 % received glyburide/metformin 1.25 mg/250 mg tablets BID , and those with an HbA1c of > or = 9 % received glyburide/metformin 2.5 mg/500 mg tablets BID . Primary efficacy variables included changes from baseline in HbA1c , fasting plasma glucose ( FPG ) , and body weight at week 52 . Safety was assessed based on adverse-event data and the results of physical examinations and laboratory tests . RESULTS A total of 828 patients were enrolled in the study : 515 who completed the 32-week double-blind study , 138 who were discontinued from the double-blind study , and 175 who were directly enrolled . At week 52 , the mean HbA1c value for the entire population had decreased from a baseline value of 8.73 % to 7.04 % ( 95 % CI , -1.81 to -1.58 ) . Patients who were enrolled directly had the poorest glycemic control at baseline and experienced the greatest reduction in HbA1c ( -3.35 % ; 95 % CI , -3.61 to -3.10 ) . A reduction in mean FPG for the total population was observed as early as week 2 , from 201 to 141 mg/dL ( 95 % CI , -63.0 to -55.7 ) . Symptoms of hypoglycemia occurred in 19.9 % ( 165/828 ) of patients , although only one third of these patients had a documented finger-stick blood glucose value of > or = 50 mg/dL. CONCLUSIONS In this 52-week , open-label extension study , glyburide/metformin tablets were well tolerated and effective in patients with type 2 diabetes . They provided rapid and sustainable reductions in HbA1c values and FPG concentrations OBJECTIVE This open-label , active-controlled study investigated the cardiac safety and antihyperglycemic effect of rosiglitazone ( RSG ) in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS Of the 203 patients r and omly assigned to RSG  ( 4 mg b.i.d . ) or glyburide ( GLB ) ( titrated to achieve optimal glycemic control for the first 8 weeks only to limit the risk of hypoglycemia ; mean 10.5 mg/day ) , 118 had an echocardiogram performed at week 52 .  Left ventricular ( LV ) mass index , ejection fraction , and left ventricular end-diastolic volume were assessed by M-mode echocardiography at baseline and weeks 12 , 28 , and 52 ; 24-h ambulatory blood pressure was assessed at baseline and at weeks 28 and 52 . Glycemic control was assessed by measuring fasting plasma glucose ( FPG ) and HbA(1c ) . RESULTS Neither treatment produced an increase in LV mass index that exceeded 1 SD . Ejection fraction did not change in either group . Both groups had clinical ly insignificant increases in LV end-diastolic volume .  RSG , but not GLB , caused a statistically significant reduction in ambulatory diastolic blood pressure . Both treatments reduced HbA(1c ) and FPG . CONCLUSIONS A total of 52 weeks of therapy with RSG ( 4 mg b.i.d . ) did not adversely affect cardiac structure or function in patients with type 2 diabetes and produced significant and sustained reductions in hyperglycemia . Decreases in ambulatory diastolic blood pressure with RSG were superior to those with GLB Background Patients with type 2 diabetes mellitus ( T2DM ) struggle with the management of their condition due to difficulty relating lifestyle behaviors with glycemic control . While self-monitoring of blood glucose ( SMBG ) has proven to be effective for those treated with insulin , it has been shown to be less beneficial for those only treated with oral medications or lifestyle modification . We hypothesized that the effective self-management of non-insulin treated T2DM requires a behavioral intervention that empowers patients with the ability to self-monitor , underst and the impact of lifestyle behaviors on glycemic control , and adjust their self-care based on context ualized SMBG data . Objective The primary objective of this r and omized controlled trial ( RCT ) is to determine the impact of bant2 , an evidence -based , patient-centered , behavioral mobile app intervention , on the self-management of T2DM . Our second postulation is that automated feedback delivered through the mobile app will be as effective , less re source intensive , and more scalable than interventions involving additional health care provider feedback . Methods This study is a 12-month , prospect i ve , multicenter RCT in which 150 participants will be r and omly assigned to one of two groups : the control group will receive current st and ard of care , and the intervention group will receive the mobile phone app system in addition to st and ard of care . The primary outcome measure is change in glycated hemoglobin A1c from baseline to 12 months . Results The first patient was enrolled on July 28 , 2015 , and we anticipate completing this study by September , 2018 . Conclusions This RCT is one of the first to evaluate an evidence -based mobile app that focuses on facilitating lifestyle behavior change driven by context ualized and structured SMBG . The results of this trial will provide insights regarding the usage of mobile tools and consumer- grade devices for diabetes self-care , the economic model of using incentives to motivate behavior change , and the consumption of test strips when following a rigorously structured approach for SMBG . Trial Registration Clinical Trials.gov NCT02370719 ; https:// clinical trials.gov/ct2/show/NCT02370719 ( Archived at http://www.webcitation.org/6jpyjfVRs Fregni F , Imamura M , Chien HF , Lew HL , Boggio P , Kaptchuk TJ , Riberto M , Hsing WT , Battistella LR , Furlan A : Challenges and recommendations for placebo controls in r and omized trials in physical and rehabilitation medicine : A report of the International Placebo Symposium Working Group . Compared with other specialties , the field of physical and rehabilitation medicine has not received the deserved recognition from clinicians and research ers in the scientific community . One of the reasons is the lack of sound evidence to support the traditional physical and rehabilitation medicine treatments . The best way to change this disadvantage is through a well conducted clinical research , such as st and ard placebo- or sham-controlled r and omized clinical trials . Therefore , having placebo groups in clinical trials is essential to improve the level of evidence -based practice in physical and rehabilitation medicine that ultimately translates to better clinical care . To address the challenges for the use of placebo in physical and rehabilitation medicine and r and omized clinical trials and to create useful recommendations , we convened a working group during the inaugural International Symposium in Placebo  ( February 2009 , in Sao Paulo , Brazil ) in which the following topics were discussed : ( 1 ) current status of r and omized clinical trials in physical and rehabilitation medicine , ( 2 ) challenges for the use of placebo in physical and rehabilitation medicine , ( 3 ) bioethics , ( 4 ) use of placebo in acupuncture trials and for the treatment of low-back pain , ( 5 ) mechanisms of placebo , and ( 6 ) insights from other specialties . The current article represents the consensus report from the working group OBJECTIVE The purpose of this study was to investigate the effect of acute and chronic whole-body vibration exercise on serum insulin-like growth factor-1 ( IGF-1 ) levels in women with fibromyalgia . METHODS A r and omized controlled two-factor mixed experimental design was used . Twenty-four women with fibromyalgia ( age + /- st and ard error of the mean , 54.95 + /- 2.03 ) were r and omized into the vibration group or the control group . The vibration group underwent a protocol of static and dynamic tasks with whole-body vibration exercise twice a week for a total of six weeks , whereas the control group performed the same protocol without vibratory stimulus . Both groups continued their usual pharmacological treatment .  Serum IGF-1 levels were determined using enzyme-linked immunosorbent assay ( ELISA ) . To test the effects of long-term whole-body vibration exercise , serum IGF-1 measurements were taken at baseline and at weeks 1 , 3 , and 6 of the intervention . To test the short-term effects , at week 1 , serum IGF-1 measurements were taken before and immediately following a session of whole-body vibration exercise . RESULTS Treatment adherence was 93 % in the vibration group and 92 % in the control group . None of the subjects dropped out of the study . There was an absence of change in IGF-1 at week 1 and week 6 of whole-body vibration exercise . CONCLUSION Results show no change in serum IGF-1 levels in women with fibromyalgia undergoing whole-body vibration exercise . Although high-intensity exercise and whole-body vibration exercise have been shown to increase serum IGF-1 in healthy individuals , the effectiveness of whole-body vibration exercise as a strategy to produce improvements in serum IGF-1 levels in women with fibromyalgia could not be demonstrated Objectives In a r and omized controlled trial , adults with Type 1 diabetes and suboptimal glycemic control who received motivational enhancement therapy ( MET ) plus cognitive behavioral therapy ( CBT )  had a greater reduction in their 12-month hemoglobin A1c ( HbA1c ) than those who received usual care ( UC ) . We tested whether improvements in glycemic control persisted up to 4 years after r and omization . Methods In the original trial , participants were r and omized to UC ( n = 121 ) , 4 sessions of MET ( n = 117 ) , or 4 sessions of MET plus 8 sessions of CBT  ( n = 106 ) . Of the 344 patients who participated in the original trial , 260 ( 75.6 % ) consented to take part in this posttrial study . A linear mixed model was fitted to available measurements to assess whether intervention effects on HbA1c at 12 months were sustained at 2 , 3 , and 4 years . Results Estimated mean HbA1c level was lower for participants in the two intervention arms when compared with UC at 2 , 3 , and 4 years , but none of the differences were statistically significant . At 4 years , estimated mean HbA1c level  for MET plus CBT was 0.28 % ( 95 % confidence interval = −0.22 % to 0.77 % ) lower than that for UC , and estimated mean HbA1c level for MET was 0.17 % ( 95 % confidence interval = −0.33 % to 0.66 % ) lower than that for UC . Conclusions There was no evidence of benefit for patients r and omized to MET plus CBT at 2 , 3 , or 4 years . Larger studies are needed to estimate long-term treatment effects with greater precision . Current models of psychological treatments in diabetes may need to be intensified or include maintenance sessions to maintain improvements in glycemic control . Abbreviations RCT = r and omized controlled trial ; MET = motivational enhancement therapy ; CBT = cognitive behavioral therapy ; UC = usual OBJECTIVE The diagnosis and treatment of youth with severe nonepisodic irritability and hyperarousal , a syndrome defined as severe mood dysregulation ( SMD ) by Leibenluft , has been the focus of increasing concern . We conducted the first r and omized double-blind , placebo-controlled trial in SMD youth , choosing lithium on the basis of its potential in treating irritability and aggression and neuro-metabolic effects . METHODS SMD youths 7 - 17 years were tapered off their medications . Those who continued to meet SMD criteria after a 2-week , single-blind , placebo run-in were r and omized to a 6-week double-blind trial of either lithium ( n = 14 ) or placebo ( n = 11 ) . Clinical outcome measures were : ( 1 ) Clinical Global Impressions-Improvement ( CGI-I ) score less than 4 at trial 's end and ( 2 ) the Positive and Negative Syndrome Scale ( PANSS ) factor 4 score . Magnetic resonance spectroscopy ( MRS ) outcome measures were myoinositol ( mI ) , N-acetyl-aspartate ( NAA ) , and combined glutamate/glutamine ( GLX ) , all referenced to creatine ( Cr ) . RESULTS In all , 45 % ( n = 20/45 ) of SMD youths were not r and omized due to significant clinical improvement during the placebo run-in . Among r and omized patients , there were no significant between-group differences in either clinical or MRS outcome measures . CONCLUSION Our study suggests that although lithium may not result in significant clinical or neurometabolic alterations in SMD youths , further SMD treatment trials are warranted given its prevalence OBJECTIVE To determine whether serum lipid intervention , in addition to conventional diabetes treatment , could alter cardiovascular outcomes in type 2 diabetes . RESEARCH DESIGN AND METHODS There were 164 type 2 diabetic subjects ( 117 men , 47 women ) without a history of clinical cardiovascular disease r and omized to receive either bezafibrate or placebo daily on a double-blind basis in addition to routine diabetes treatment and followed prospect ively for a minimum of 3 years . Serial biochemical and noninvasive vascular assessment s , carotid and femoral artery B-mode ultrasound measurements , and those pertaining to coronary heart disease (CHD)— clinical history , the World Health Organization ( WHO ) cardiovascular question naire , and resting and exercise electrocardiogram (ECG)—were recorded . RESULTS Bezafibrate treatment was associated with significantly greater reductions over 3 years in median serum triglyceride ( −32 vs. 4 % , P = 0.001 ) , total cholesterol ( −7 vs. −0.3 % , P = 0.004 ) , and total−to-HDL cholesterol ratio ( −12 vs. −0.0 % , P = 0.001 ) , and an increase in HDL cholesterol ( 6 vs. −2 % , P = 0.02 ) as compared with placebo . There was a trend toward a greater reduction of fibrinogen ( −18 vs. −6 % , P = 0.08 ) at 3 years . No significant differences between the two groups were found in the progress of ultrasonically measured arterial disease . In those treated with bezafibrate , there was a significant reduction ( P = 0.01 , log-rank test ) in the combined incidence of Minnesota-coded probable ischemic change on the resting ECG and of documented myocardial infa rct ion . CONCLUSIONS Improving dyslipidemia in type 2 diabetic subjects had no effect on the progress of ultrasonically measured arterial disease , although the lower rate of “ definite CHD events ” in the treated group suggests that this might result in a reduction in the incidence of coronary heart disease
Conclusion : This meta‐ analysis has shown that fibrate treatment  significantly decreases fasting plasma glucose , insulin levels , and HOMA‐IR indicating additional clinical therapeutic benefits .
Aims : The aim of this meta‐ analysis of r and omized placebo‐controlled clinical trials was to assess the effect of fibrates on glycemic parameters .