Zonisamide for Weight Reduction in Obese Adults

Study Overview
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Brief Summary
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The primary aim of this study is to assess long-term weight loss efficacy of zonisamide relative to placebo in obese patients prescribed a dietary intervention.

Detailed Description
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This RCT compares two doses of zonisamide and placebo for one year. A total of 225 subjects are randomly assigned to one of the three treatment interventions at Duke University Medical Centre. The primary outcome measure is change in body weight in kilograms. Secondary outcomes include changes in waist circumference, glycaemic and inflammatory markers, lipids, food craving, hunger and satiety, quality of life, blood pressure and heart rate.

Official Title
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Zonisamide for Weight Reduction in Obese Adults

Conditions
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Obesity

Intervention / Treatment
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* Drug: Zonisamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-65 years; BMI 30-50 Exclusion Criteria: Secondary obesity; Significant cardiovascular disease; Stroke, seizure disorder or other significant neurological disease; Significant liver or gallbladder disease; Significant renal disease or history of kidney stones; HIV positive status; Diabetes mellitus; Untreated or unstable hypothyroidism Malignancy in the past 5 years; Concomitant medications that cause significant weight gain or weight loss; Concomitant use of prescription or OTC weight loss medications; Had bariatric surgery or planning surgery in the next 1 year; Weight change of more than 4 kg in the past 3 months; Suicidal subjects; Major depression in the past 6 months; History of psychosis, bipolar disorder, or severe personality disorders; Subjects taking antipsychotics or mood stabilisers; Alcohol or substance abuse in the past 6 months; Currently taking zonisamide or other antiepileptic drugs; History of hypersensitivity to zonisamide or sulfonamides; Pregnant or planning pregnancy in the next year, or breastfeeding; Severe physical disability; Current participation in a commercial weight loss program or planning to participate; Currently following low-carbohydrate, high protein, high fat diet; Use of investigational medications or devices (current or past 4 weeks) -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Zonisamide 400 mg | Drug: Zonisamide<br>* zonisamide 400 mg, 200 mg, or placebo<br>|
| Experimental: B<br>Zonisamide 200 mg | Drug: Zonisamide<br>* zonisamide 400 mg, 200 mg, or placebo<br>|
| Placebo Comparator: C<br>matching placebo | Drug: Zonisamide<br>* zonisamide 400 mg, 200 mg, or placebo<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportions of Patients With 5% Weight Loss | 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. | 1 year | 
| Proportions of Patients With 10% Weight Loss | This outcomes measure followed the same principles at measurement of proportions of patients with 5% weight loss described elsewhere. | 1 year | 
| Waist Circumference | 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. | 1 year | 
| Inflammatory Markers (CRP) | C reactive Protein (CRP) | 1 year | 
| Change in Lipids |  | baseline, 1 year | 
| Quality of Life as Measured by HADS_D | 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. | 1 year | 
| Change in Blood Pressure |  | Baseline, 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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obesity treatment, weight loss, antiobesity drugs, zonisamide