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Zonisamide for Weight Reduction in Obese Adults

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00275834
First Posted: January 12, 2006
Last Update Posted: January 12, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Duke University
Results First Submitted: December 10, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Obesity
Intervention: Drug: Zonisamide

  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
The study was conducted at Duke University Medical Center between 2006 and 2011.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants are considered to have completed the study if they returned for final study visit. The number completed represents participants who stayed on study drug during the trial plus participants who discontinued study drug during the trial but continued to be followed by study team and completed the final visit assessments.

Reporting Groups
  Description
Placebo

Zonisamide 100 mg and placebo capsules were prepared in accordance with Good Manufacturing Practice (GMP) guidelines in Duke Compounding Facility with active pharmaceutical ingredient (Sochinaz SA, Switzerland, distributed by Bachem Americas, King of Prussia, Pennsylvania) plus dextrose as an inactive ingredient. Identical-looking placebo capsules contained dextrose.

Each capsule contained zonisamide 100 mg or placebo, with patients and study staff blinded to contents. Dose was gradually titrated upward as follows: 1 capsule for 15 days, 2 during days 16-30, 3 capsules during days 31-45, and 4 from day 46 onward. The entire dose was taken at night. Blinded dose reduction was allowed and dose increase could be withheld. Patients had the option to discontinue the drug and remain in the study receiving only diet and lifestyle counseling.

Zonisamide 200 mg Dosing of matching placebo was identical.
Zonisamide 400 mg No text entered.

Participant Flow:   Overall Study
    Placebo   Zonisamide 200 mg   Zonisamide 400 mg
STARTED   74   76   75 
Completed Study While on Study Drug   54   51   62 
COMPLETED   71   73   74 
NOT COMPLETED   3   3   1 



  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 No text entered.
Zonisamide 200 mg No text entered.
Zonisamide 400 mg No text entered.
Total Total of all reporting groups

Baseline Measures
   Placebo   Zonisamide 200 mg   Zonisamide 400 mg   Total 
Overall Participants Analyzed 
[Units: Participants]
 74   76   75   225 
Age 
[Units: Participants]
Count of Participants
       
<=18 years      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Between 18 and 65 years      74 100.0%      76 100.0%      75 100.0%      225 100.0% 
>=65 years      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Age 
[Units: Years]
Mean (Standard Deviation)
 43.5  (10.3)   44.2  (10.1)   42.3  (10.0)   43.4  (10.1) 
Gender 
[Units: Participants]
Count of Participants
       
Female      44  59.5%      45  59.2%      45  60.0%      134  59.6% 
Male      30  40.5%      31  40.8%      30  40.0%      91  40.4% 
Region of Enrollment 
[Units: Participants]
       
United States   74   76   75   225 


  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Change in Body Weight   [ Time Frame: 1 year ]

Measure Type Primary
Measure Title Change in Body Weight
Measure Description The primary endpoint was weight loss at 1-year, Month-12 weight minus baseline weight, in kilograms.
Time Frame 1 year  

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.
intent-to-treat

Reporting Groups
  Description
Placebo No text entered.
Zonisamide 200 mg No text entered.
Zonisamide 400 mg No text entered.

Measured Values
   Placebo   Zonisamide 200 mg   Zonisamide 400 mg 
Participants Analyzed 
[Units: Participants]
 74   76   75 
Change in Body Weight 
[Units: Kg]
Mean (95% Confidence Interval)
 -4.0 
 (-5.8 to -2.3) 
 -4.4 
 (-6.1 to -2.6) 
 -7.3 
 (-9.0 to -5.6) 

No statistical analysis provided for Change in Body Weight



2.  Secondary:   Proportions of Patients With 5% Weight Loss   [ Time Frame: 1 year ]

Measure Type Secondary
Measure Title Proportions of Patients With 5% Weight Loss
Measure Description These were the proportions of patients losing 5% or more weight at 1-year relative to baseline. The measures were modeled with logistic regressions that included the three-level group proxy and a baseline weight covariate.
Time Frame 1 year  

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 No text entered.
Zonisamide 200 mg No text entered.
Zonisamide 400 mg No text entered.

Measured Values
   Placebo   Zonisamide 200 mg   Zonisamide 400 mg 
Participants Analyzed 
[Units: Participants]
 74   76   75 
Proportions of Patients With 5% Weight Loss 
[Units: Participants]
 23   26   41 

No statistical analysis provided for Proportions of Patients With 5% Weight Loss



3.  Secondary:   Proportions of Patients With 10% Weight Loss   [ Time Frame: 1 year ]

Measure Type Secondary
Measure Title Proportions of Patients With 10% Weight Loss
Measure Description This outcomes measure followed the same principles at measurement of proportions of patients with 5% weight loss described elsewhere.
Time Frame 1 year  

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 No text entered.
Zonisamide 200 mg No text entered.
Zonisamide 400 mg No text entered.

Measured Values
   Placebo   Zonisamide 200 mg   Zonisamide 400 mg 
Participants Analyzed 
[Units: Participants]
 74   76   75 
Proportions of Patients With 10% Weight Loss 
[Units: Participants]
 6   17   24 

No statistical analysis provided for Proportions of Patients With 10% Weight Loss



4.  Secondary:   Waist Circumference   [ Time Frame: 1 year ]

Measure Type Secondary
Measure Title Waist Circumference
Measure Description Analyses was based on intent-to-treat ANCOVA. Difference scores from baseline to endpoint (Month-12) for each measure were regressed on the three-level proxy denoting group while controlling for the baseline value of the same measure. Contrasts were subsequently estimated in models, which had a significant overall treatment effect.
Time Frame 1 year  

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.
intent-to-treat

Reporting Groups
  Description
Placebo No text entered.
Zonisamide 200 mg No text entered.
Zonisamide 400 mg No text entered.

Measured Values
   Placebo   Zonisamide 200 mg   Zonisamide 400 mg 
Participants Analyzed 
[Units: Participants]
 74   76   75 
Waist Circumference 
[Units: Cm]
Mean (95% Confidence Interval)
 -4.8 
 (-6.6 to -3.1) 
 -6.1 
 (-7.8 to -4.3) 
 -8.5 
 (-10.2 to -6.8) 

No statistical analysis provided for Waist Circumference



5.  Secondary:   Inflammatory Markers (CRP)   [ Time Frame: 1 year ]

Measure Type Secondary
Measure Title Inflammatory Markers (CRP)
Measure Description C reactive Protein (CRP)
Time Frame 1 year  

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 had CRP testing completed

Reporting Groups
  Description
Placebo No text entered.
Zonisamide 200 mg No text entered.
Zonisamide 400 mg No text entered.

Measured Values
   Placebo   Zonisamide 200 mg   Zonisamide 400 mg 
Participants Analyzed 
[Units: Participants]
 73   75   75 
Inflammatory Markers (CRP) 
[Units: mg/L]
Mean (Standard Error)
 0.523  (0.064)   0.536  (0.06)   0.443  (0.044) 

No statistical analysis provided for Inflammatory Markers (CRP)



6.  Secondary:   Change in Lipids   [ Time Frame: baseline, 1 year ]

Measure Type Secondary
Measure Title Change in Lipids
Measure Description No text entered.
Time Frame baseline, 1 year  

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

Zonisamide 100 mg and placebo capsules were prepared in accordance with Good Manufacturing Practice (GMP) guidelines in Duke Compounding Facility with active pharmaceutical ingredient (Sochinaz SA, Switzerland, distributed by Bachem Americas, King of Prussia, Pennsylvania) plus dextrose as an inactive ingredient. Identical-looking placebo capsules contained dextrose.

Each capsule contained zonisamide 100 mg or placebo, with patients and study staff blinded to contents. Dose was gradually titrated upward as follows: 1 capsule for 15 days, 2 during days 16-30, 3 capsules during days 31-45, and 4 from day 46 onward. The entire dose was taken at night. Blinded dose reduction was allowed and dose increase could be withheld. Patients had the option to discontinue the drug and remain in the study receiving only diet and lifestyle counseling.

Zonisamide 200 mg Dosing of matching placebo was identical.
Zonisamide 400 mg No text entered.

Measured Values
   Placebo   Zonisamide 200 mg   Zonisamide 400 mg 
Participants Analyzed 
[Units: Participants]
 74   76   75 
Change in Lipids 
[Units: mg/dL]
Least Squares Mean (95% Confidence Interval)
     
Total Cholesterol   -1.9 
 (-7.2 to 3.4) 
 4.1 
 (-1.0 to 9.2) 
 -0.1 
 (-5.0 to 4.9) 
LDL Cholesterol   -2.0 
 (-6.7 to 2.7) 
 1.7 
 (-2.8 to 6.3) 
 -0.3 
 (-4.7 to 4.1) 
HDL Cholesterol   2.5 
 (0.7 to 4.3) 
 1.5 
 (-0.3 to 3.2) 
 3.4 
 (1.7 to 5.1) 
Triglycerides   -11.3 
 (-22.6 to 0.0) 
 0.7 
 (-10.1 to 11.5) 
 -11.7 
 (-22.2 to -1.1) 

No statistical analysis provided for Change in Lipids



7.  Secondary:   Quality of Life as Measured by HADS_D   [ Time Frame: 1 year ]

Measure Type Secondary
Measure Title Quality of Life as Measured by HADS_D
Measure Description Hospital Anxiety and Depression Scale - Depression (HADS-D) The HADS is a 14-item self-administered questionnaire that consists of 2 scales, one measuring anxiety (HADS-A), and the other measuring depression (HADS-D). Each subscale consists of 7 statements and the participant responds as to how each item applies to him/her over the past week on 4-point response scale. Separate scores are calculated for anxiety and depression and a score (ranging from 0 to 21) is obtained for each subscale. The higher the score, the more severe the anxiety or depression.
Time Frame 1 year  

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 No text entered.
Zonisamide 200 mg No text entered.
Zonisamide 400 mg No text entered.

Measured Values
   Placebo   Zonisamide 200 mg   Zonisamide 400 mg 
Participants Analyzed 
[Units: Participants]
 74   76   75 
Quality of Life as Measured by HADS_D 
[Units: Units on a scale]
Least Squares Mean (95% Confidence Interval)
 2.12 
 (1.54 to 2.70) 
 2.76 
 (2.18 to 3.33) 
 1.95 
 (1.38 to 2.53) 

No statistical analysis provided for Quality of Life as Measured by HADS_D



8.  Secondary:   Change in Blood Pressure   [ Time Frame: Baseline, 1 year ]

Measure Type Secondary
Measure Title Change in Blood Pressure
Measure Description No text entered.
Time Frame Baseline, 1 year  

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

Zonisamide 100 mg and placebo capsules were prepared in accordance with Good Manufacturing Practice (GMP) guidelines in Duke Compounding Facility with active pharmaceutical ingredient (Sochinaz SA, Switzerland, distributed by Bachem Americas, King of Prussia, Pennsylvania) plus dextrose as an inactive ingredient. Identical-looking placebo capsules contained dextrose.

Each capsule contained zonisamide 100 mg or placebo, with patients and study staff blinded to contents. Dose was gradually titrated upward as follows: 1 capsule for 15 days, 2 during days 16-30, 3 capsules during days 31-45, and 4 from day 46 onward. The entire dose was taken at night. Blinded dose reduction was allowed and dose increase could be withheld. Patients had the option to discontinue the drug and remain in the study receiving only diet and lifestyle counseling.

Zonisamide 200 mg Dosing of matching placebo was identical.
Zonisamide 400 mg No text entered.

Measured Values
   Placebo   Zonisamide 200 mg   Zonisamide 400 mg 
Participants Analyzed 
[Units: Participants]
 74   76   75 
Change in Blood Pressure 
[Units: Mm Hg]
Least Squares Mean (95% Confidence Interval)
     
Systolic   -0.6 
 (-2.9 to 1.6) 
 -4.4 
 (-6.7 to -2.1) 
 -1.9 
 (-4.1 to 0.4) 
Diastolic   -1.5 
 (-3.2 to 0.1) 
 -3.6 
 (-5.3 to -2.0) 
 -3.9 
 (-5.5 to -2.3) 

No statistical analysis provided for Change in Blood Pressure




  Serious Adverse Events


  Other Adverse Events


  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
No text entered.


  More Information