Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

The Use of Metformin in the Treatment of Antipsychotic-Induced Weight Gain in Schizophrenia (The METS Study)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier:
NCT00816907
First received: January 2, 2009
Last updated: February 13, 2013
Last verified: November 2010
Results First Received: January 3, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Schizophrenia
Interventions: Drug: Metformin
Drug: Placebo

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
A randomized, double-blind, placebo-controlled multicenter trial conducted between March 2009 and February 2010 at 17 academic, veterans affairs, and private research clinics. 146 clinically stable overweight outpatients with chronic schizophrenia and schizoaffective disorder were enrolled.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Prior to randomization prospective participants were screened for eligibility

Reporting Groups
  Description
Placebo Matching over-encapsulated placebo pills
Metformin Metformin 500 mg pills over-encapsulated up to 4 pills daily as tolerated

Participant Flow:   Overall Study
    Placebo     Metformin  
STARTED     71     75  
COMPLETED     58     58  
NOT COMPLETED     13     17  



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Placebo Matching over-encapsulated placebo pills
Metformin Metformin 500 mg pills over-encapsulated up to 4 pills daily as tolerated
Total Total of all reporting groups

Baseline Measures
    Placebo     Metformin     Total  
Number of Participants  
[units: participants]
  71     75     146  
Age  
[units: years]
Mean ± Standard Deviation
  45.0  ± 10.3     41.4  ± 11.5     43.2  ± 11.1  
Gender  
[units: participants]
     
Female     22     23     45  
Male     49     52     101  



  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Mean Difference in Body Weight Change Between Participants Assigned to Metformin and Participants Assigned to Placebo   [ Time Frame: Measured at the last study visit ]

Measure Type Primary
Measure Title Mean Difference in Body Weight Change Between Participants Assigned to Metformin and Participants Assigned to Placebo
Measure Description Mean difference in body weight change between participants assigned to metformin and participants assigned to placebo from baseline to last study visit (up to 16 weeks)
Time Frame Measured at the last study visit  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Evaluable population that took assigned study treatment

Reporting Groups
  Description
Placebo Matching over-encapsulated placebo pills
Metformin Metformin 500 mg pills over-encapsulated up to 4 pills daily as tolerated

Measured Values
    Placebo     Metformin  
Number of Participants Analyzed  
[units: participants]
  71     75  
Mean Difference in Body Weight Change Between Participants Assigned to Metformin and Participants Assigned to Placebo  
[units: kilograms]
Mean ( 95% Confidence Interval )
  -1.0  
  ( -2.0 to -0.0 )  
  -3.0  
  ( -4.0 to -2.0 )  

No statistical analysis provided for Mean Difference in Body Weight Change Between Participants Assigned to Metformin and Participants Assigned to Placebo



2.  Secondary:   Change in Total Cholesterol From Baseline to 16 Weeks   [ Time Frame: 16 weeks ]

Measure Type Secondary
Measure Title Change in Total Cholesterol From Baseline to 16 Weeks
Measure Description Total cholesterol
Time Frame 16 weeks  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
randomized participants who took assigned treatment

Reporting Groups
  Description
Placebo No text entered.
Metformin No text entered.

Measured Values
    Placebo     Metformin  
Number of Participants Analyzed  
[units: participants]
  71     75  
Change in Total Cholesterol From Baseline to 16 Weeks  
[units: mg/dL]
Mean ( 95% Confidence Interval )
  0.2  
  ( -6.5 to 6.9 )  
  -8.9  
  ( -15.6 to -2.3 )  

No statistical analysis provided for Change in Total Cholesterol From Baseline to 16 Weeks



3.  Secondary:   Change in HDL Cholesterol From Baseline to 16 Weeks   [ Time Frame: 16 weeks ]

Measure Type Secondary
Measure Title Change in HDL Cholesterol From Baseline to 16 Weeks
Measure Description high-density lipoprotein
Time Frame 16 weeks  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
randomized participants who took assigned treatment

Reporting Groups
  Description
Placebo No text entered.
Metformin No text entered.

Measured Values
    Placebo     Metformin  
Number of Participants Analyzed  
[units: participants]
  71     75  
Change in HDL Cholesterol From Baseline to 16 Weeks  
[units: mg/dL]
Least Squares Mean ( 95% Confidence Interval )
  -0.4  
  ( -2.3 to 1.4 )  
  -0.6  
  ( -2.4 to 1.2 )  

No statistical analysis provided for Change in HDL Cholesterol From Baseline to 16 Weeks



4.  Secondary:   Change in LDL Cholesterol From Baseline to 16 Weeks   [ Time Frame: 16 weeks ]

Measure Type Secondary
Measure Title Change in LDL Cholesterol From Baseline to 16 Weeks
Measure Description low-density lipoprotein
Time Frame 16 weeks  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
participants who took assigned treatment

Reporting Groups
  Description
Placebo No text entered.
Metformin No text entered.

Measured Values
    Placebo     Metformin  
Number of Participants Analyzed  
[units: participants]
  71     75  
Change in LDL Cholesterol From Baseline to 16 Weeks  
[units: mg/dL]
Least Squares Mean ( 95% Confidence Interval )
  -2.0  
  ( -7.7 to 3.7 )  
  -7.1  
  ( -12.6 to -1.5 )  

No statistical analysis provided for Change in LDL Cholesterol From Baseline to 16 Weeks



5.  Secondary:   Change in Triglycerides From Baseline to 16 Weeks   [ Time Frame: 16 weeks ]

Measure Type Secondary
Measure Title Change in Triglycerides From Baseline to 16 Weeks
Measure Description serum triglycerides
Time Frame 16 weeks  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
participants who took assigned treatment

Reporting Groups
  Description
Placebo No text entered.
Metformin No text entered.

Measured Values
    Placebo     Metformin  
Number of Participants Analyzed  
[units: participants]
  71     75  
Change in Triglycerides From Baseline to 16 Weeks  
[units: mg/dL]
Least Squares Mean ( 95% Confidence Interval )
  13.2  
  ( -0.3 to 26.7 )  
  -7.0  
  ( -20.4 to 6.3 )  

No statistical analysis provided for Change in Triglycerides From Baseline to 16 Weeks



6.  Secondary:   Change in Fasting Glucose From Baseline to 16 Weeks   [ Time Frame: 16 weeks ]

Measure Type Secondary
Measure Title Change in Fasting Glucose From Baseline to 16 Weeks
Measure Description fasting blood glucose
Time Frame 16 weeks  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
participants who took assigned treatment

Reporting Groups
  Description
Placebo No text entered.
Metformin No text entered.

Measured Values
    Placebo     Metformin  
Number of Participants Analyzed  
[units: participants]
  71     75  
Change in Fasting Glucose From Baseline to 16 Weeks  
[units: mg/dL]
Least Squares Mean ( 95% Confidence Interval )
  -1.6  
  ( -4.3 to 1.2 )  
  -2.3  
  ( -5.0 to 0.5 )  

No statistical analysis provided for Change in Fasting Glucose From Baseline to 16 Weeks



7.  Secondary:   Change in Fasting Insulin From Baseline to 16 Weeks   [ Time Frame: 16 weeks ]

Measure Type Secondary
Measure Title Change in Fasting Insulin From Baseline to 16 Weeks
Measure Description Fasting insulin
Time Frame 16 weeks  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
participants who took assigned treatment

Reporting Groups
  Description
Placebo No text entered.
Metformin No text entered.

Measured Values
    Placebo     Metformin  
Number of Participants Analyzed  
[units: participants]
  71     75  
Change in Fasting Insulin From Baseline to 16 Weeks  
[units: mU/L]
Mean ( 95% Confidence Interval )
  5.5  
  ( -1.7 to 12.6 )  
  1.6  
  ( -5.5 to 8.6 )  

No statistical analysis provided for Change in Fasting Insulin From Baseline to 16 Weeks



8.  Secondary:   Change in Hemoglobin A1c From Baseline to 16 Weeks   [ Time Frame: 16 weeks ]

Measure Type Secondary
Measure Title Change in Hemoglobin A1c From Baseline to 16 Weeks
Measure Description glycosylated hemoglobin
Time Frame 16 weeks  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
participants who took assigned treatment

Reporting Groups
  Description
Placebo No text entered.
Metformin No text entered.

Measured Values
    Placebo     Metformin  
Number of Participants Analyzed  
[units: participants]
  71     75  
Change in Hemoglobin A1c From Baseline to 16 Weeks  
[units: percent]
Least Squares Mean ( 95% Confidence Interval )
  0.01  
  ( -0.04 to 0.06 )  
  -0.06  
  ( -0.11 to -0.01 )  

No statistical analysis provided for Change in Hemoglobin A1c From Baseline to 16 Weeks




  Serious Adverse Events


  Other Adverse Events
  Hide Other Adverse Events

Time Frame No text entered.
Additional Description No text entered.

Frequency Threshold
Threshold above which other adverse events are reported   5%  

Reporting Groups
  Description
Placebo Matching over-encapsulated placebo pills
Metformin Metformin 500 mg pills over-encapsulated up to 4 pills daily as tolerated

Other Adverse Events
    Placebo     Metformin  
Total, other (not including serious) adverse events      
# participants affected / at risk     33/71     40/75  
Gastrointestinal disorders      
diarrhea    
# participants affected / at risk     12/71 (16.90%)     25/75 (33.33%)  
# events     12     25  
nausea    
# participants affected / at risk     8/71 (11.27%)     12/75 (16.00%)  
# events     8     12  
abdominal discomfort    
# participants affected / at risk     9/71 (12.68%)     12/75 (16.00%)  
# events     9     12  
nausea    
# participants affected / at risk     8/71 (11.27%)     12/75 (16.00%)  
# events     8     12  
vomiting    
# participants affected / at risk     3/71 (4.23%)     8/75 (10.67%)  
# events     3     8  
Musculoskeletal and connective tissue disorders      
Muscle pain    
# participants affected / at risk     10/71 (14.08%)     13/75 (17.33%)  
# events     10     13  
weakness    
# participants affected / at risk     6/71 (8.45%)     8/75 (10.67%)  
# events     6     8  
Nervous system disorders      
headache    
# participants affected / at risk     17/71 (23.94%)     11/75 (14.67%)  
# events     17     11  
Events were collected by systematic assessment



  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Changes over periods of more than 16 weeks are unknown.


  More Information