Zonisamide for Weight Reduction in Obese Adults

• Proportions of Patients With 5% Weight Loss [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  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.
• Proportions of Patients With 10% Weight Loss [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  This outcomes measure followed the same principles at measurement of proportions of patients with 5% weight loss described elsewhere.
• Waist Circumference [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  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.
• Inflammatory Markers [ Time Frame: 1 year ] [ Designated as safety issue: No ]
• Lipids [ Time Frame: 1 year ] [ Designated as safety issue: No ]
• Quality of Life [ Time Frame: 1 year ] [ Designated as safety issue: No ]
• Psychological Measures [ Time Frame: 1 year ] [ Designated as safety issue: No ]
• Blood Pressure [ Time Frame: 1 year ] [ Designated as safety issue: No ]

• Proportions of patients with 5% and 10% weight loss
• Waist circumference
• Glycaemic indices
• Inflammatory markers
• Lipids
• Quality of life
• Psychological measures
• Blood pressure

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.

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.

• Experimental: A
  Zonisamide 400 mg
  Intervention: Drug: Zonisamide
• Experimental: B
  Zonisamide 200 mg
  Intervention: Drug: Zonisamide
• Placebo Comparator: C
  matching placebo
  Intervention: Drug: Zonisamide

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)

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