Obesity
Conditions
Keywords
obesity treatment, weight loss, antiobesity drugs, zonisamide
Brief summary
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
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.
Interventions
DRUGZonisamide
zonisamide 400 mg, 200 mg, or placebo
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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) \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Body Weight | 1 year | The primary endpoint was weight loss at 1-year, Month-12 weight minus baseline weight, in kilograms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportions of Patients With 10% Weight Loss | 1 year | This outcomes measure followed the same principles at measurement of proportions of patients with 5% weight loss described elsewhere. |
| Waist Circumference | 1 year | 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 (CRP) | 1 year | C reactive Protein (CRP) |
| Proportions of Patients With 5% Weight Loss | 1 year | 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. |
| Quality of Life as Measured by HADS_D | 1 year | 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. |
| Change in Blood Pressure | Baseline, 1 year | — |
| Change in Lipids | baseline, 1 year | — |
Countries
United States
Participant flow
Recruitment details
The study was conducted at Duke University Medical Center between 2006 and 2011.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Placebo | 74 |
| Zonisamide 200 mg | 76 |
| Zonisamide 400 mg | 75 |
| Total | 225 |
Baseline characteristics
| Characteristic | Zonisamide 200 mg | Zonisamide 400 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 76 Participants | 75 Participants | 74 Participants | 225 Participants |
| Age, Continuous | 44.2 years STANDARD_DEVIATION 10.1 | 42.3 years STANDARD_DEVIATION 10 | 43.5 years STANDARD_DEVIATION 10.3 | 43.4 years STANDARD_DEVIATION 10.1 |
| Gender Female | 45 Participants | 45 Participants | 44 Participants | 134 Participants |
| Gender Male | 31 Participants | 30 Participants | 30 Participants | 91 Participants |
| Region of Enrollment United States | 76 participants | 75 participants | 74 participants | 225 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 30 / 74 | 37 / 76 | 39 / 75 |
| serious Total, serious adverse events | 0 / 74 | 0 / 76 | 0 / 75 |
Outcome results
Primary
Change in Body Weight
The primary endpoint was weight loss at 1-year, Month-12 weight minus baseline weight, in kilograms.
Time frame: 1 year
Population: intent-to-treat
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Change in Body Weight | -4.0 kg |
| Zonisamide 200 mg | Change in Body Weight | -4.4 kg |
| Zonisamide 400 mg | Change in Body Weight | -7.3 kg |
Secondary
Change in Blood Pressure
Time frame: Baseline, 1 year
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Change in Blood Pressure | Systolic | -0.6 mm Hg |
| Placebo | Change in Blood Pressure | Diastolic | -1.5 mm Hg |
| Zonisamide 200 mg | Change in Blood Pressure | Systolic | -4.4 mm Hg |
| Zonisamide 200 mg | Change in Blood Pressure | Diastolic | -3.6 mm Hg |
| Zonisamide 400 mg | Change in Blood Pressure | Systolic | -1.9 mm Hg |
| Zonisamide 400 mg | Change in Blood Pressure | Diastolic | -3.9 mm Hg |
Secondary
Change in Lipids
Time frame: baseline, 1 year
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Change in Lipids | Total Cholesterol | -1.9 mg/dL |
| Placebo | Change in Lipids | LDL Cholesterol | -2.0 mg/dL |
| Placebo | Change in Lipids | HDL Cholesterol | 2.5 mg/dL |
| Placebo | Change in Lipids | Triglycerides | -11.3 mg/dL |
| Zonisamide 200 mg | Change in Lipids | Triglycerides | 0.7 mg/dL |
| Zonisamide 200 mg | Change in Lipids | Total Cholesterol | 4.1 mg/dL |
| Zonisamide 200 mg | Change in Lipids | HDL Cholesterol | 1.5 mg/dL |
| Zonisamide 200 mg | Change in Lipids | LDL Cholesterol | 1.7 mg/dL |
| Zonisamide 400 mg | Change in Lipids | Triglycerides | -11.7 mg/dL |
| Zonisamide 400 mg | Change in Lipids | LDL Cholesterol | -0.3 mg/dL |
| Zonisamide 400 mg | Change in Lipids | HDL Cholesterol | 3.4 mg/dL |
| Zonisamide 400 mg | Change in Lipids | Total Cholesterol | -0.1 mg/dL |
Secondary
Inflammatory Markers (CRP)
C reactive Protein (CRP)
Time frame: 1 year
Population: Participants who had CRP testing completed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Inflammatory Markers (CRP) | 0.523 mg/L | Standard Error 0.064 |
| Zonisamide 200 mg | Inflammatory Markers (CRP) | 0.536 mg/L | Standard Error 0.06 |
| Zonisamide 400 mg | Inflammatory Markers (CRP) | 0.443 mg/L | Standard Error 0.044 |
Secondary
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.
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Proportions of Patients With 10% Weight Loss | 6 participants |
| Zonisamide 200 mg | Proportions of Patients With 10% Weight Loss | 17 participants |
| Zonisamide 400 mg | Proportions of Patients With 10% Weight Loss | 24 participants |
Secondary
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.
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Proportions of Patients With 5% Weight Loss | 23 participants |
| Zonisamide 200 mg | Proportions of Patients With 5% Weight Loss | 26 participants |
| Zonisamide 400 mg | Proportions of Patients With 5% Weight Loss | 41 participants |
Secondary
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.
Time frame: 1 year
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Quality of Life as Measured by HADS_D | 2.12 units on a scale |
| Zonisamide 200 mg | Quality of Life as Measured by HADS_D | 2.76 units on a scale |
| Zonisamide 400 mg | Quality of Life as Measured by HADS_D | 1.95 units on a scale |
Secondary
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.
Time frame: 1 year
Population: intent-to-treat
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Waist Circumference | -4.8 cm |
| Zonisamide 200 mg | Waist Circumference | -6.1 cm |
| Zonisamide 400 mg | Waist Circumference | -8.5 cm |