A Study Using Functional Magnetic Resonance Imaging (fMRI) to Assess the Effects of Naltrexone SR/ Bupropion SR Therapy in Overweight or Obese Subjects

January 5, 2015 updated by: Orexigen Therapeutics, Inc

Naltrexone Sustained Release (SR) 32 mg and Bupropion Sustained Release (SR) 360 mg Combination Therapy in Functional Magnetic Resonance Imaging (fMRI) Changes in Overweight or Obese Subjects

The purpose of this study was to assess the effect of naltrexone SR/bupropion SR (NB) on brain function in response to food cues using functional magnetic resonance imaging in overweight or obese subjects.

Study Overview

Study Type

Interventional

Enrollment (Actual)

46

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • New York
      • Upton, New York, United States, 11973
        • Brookhaven National Laboratory Medical Department

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Right-handed, female subjects, 18 to 45 years of age
  • Body mass index (BMI) ≥ 27 and ≤ 40 kg/m²
  • Free from clinically significant illness or disease as determined by medical history and physical examination
  • Able to provide proof of identity during the enrollment process
  • In good general health, without clinically significant medical history, physical examination findings or laboratory results
  • Laboratory values obtained within 30 days of study entry within normal range for healthy volunteers.
  • Normal urinalysis on initial screening day defined as: negative glucose, negative or trace protein, and negative or trace hemoglobin
  • Normotensive (systolic ≤140 mm Hg, diastolic ≤90 mm hg)
  • On no concomitant medications with the exception of oral contraceptives, vitamins, and over the counter pain, indigestion or allergy medication
  • All women of child bearing potential must be non-lactating, must have a negative STAT pregnancy test, and agree to use effective contraception methods throughout study period and for 30 days after discontinuation of study drug. The following are considered effective methods of contraception: Combination or progestin-only birth control pills (oral contraceptives), vaginal contraceptive rings, contraceptive patches, Depo Provera, intrauterine devices, barrier methods with spermicide (condom/foam, diaphragm/ spermicide), abstinence. (Subjects who have had a tubal ligation, hysterectomy or are post-menopausal for 2 years are considered NOT to be of child bearing potential)
  • For women not using hormonal methods of contraception, should be in the follicular phase of the menstrual cycle at the baseline visit.
  • Non-smoker and no use of tobacco or nicotine products for at least 6 months prior to baseline. On screening and study days, we will test the subjects' urine for presence of nicotinine/cotinine (STAT) test as confirmatory evidence of being a non-smoker in addition to their self-report. A Tobacco Questionnaire and Breath CO will also be administered for eligibility on the day of screening for confirmation purposes.
  • No clinically significant abnormality on ECG, baseline QTc <470
  • Able to comply with all required study procedures
  • Available for follow up for the duration of the study
  • Willing and able to give written informed consent

Exclusion Criteria:

  • Obesity of known endocrine or genetic origin (e.g., untreated hypothyroidism, Cushing's syndrome, Prader Willi Syndrome, established Polycystic Ovary Syndrome)
  • Inability to participate in fMRI scanning sessions
  • History of occupational exposure to metal flakes in their bodies or eyes.
  • History of known indwelling ferromagnetic metals or fragments.
  • History of acute or chronic illness that requires medical therapy including active gastrointestinal conditions that might interfere with drug absorption
  • History or presence of hepatic, renal, cardiovascular or gastrointestinal diseases
  • Type I or Type II diabetes mellitus requiring pharmacotherapy
  • Active malignancy or history of malignancy (other than non-melanoma skin cancer or surgically cured cervical cancer) within 5 years of enrollment
  • Serious psychiatric illness, including lifetime history of psychiatric hospitalization, suicide attempt, bipolar disorder, schizophrenia or other psychosis, bulimia, or anorexia nervosa; current serious personality disorder, (e.g. borderline or antisocial), major depressive disorder within the previous two years, suicidal ideation or need for psychiatric treatment in the previous 6 months.
  • In need of medications for the treatment of a psychiatric disorder within the previous 6 months prior to randomization.
  • IDS-SR total score >25 or scores >1 in items 5 (sadness), 6 (irritability), 7 (anxiety/tension) or 18 (suicidality)
  • History of alcohol or drug abuse, current or within 2 years
  • Unable to abstain from caffeinated product consumption for at least 48 hours
  • History of surgical intervention for obesity
  • Use of drugs, herbs, or dietary supplements believed to significantly affect body weight or participation in a weight loss management program within one month prior to randomization.
  • History of hypersensitivity to bupropion or naltrexone
  • History of seizure disorder or predisposition to seizures (e.g., history of cerebrovascular accident, brain surgery, head trauma with ≥5 minutes loss of consciousness, concussion symptoms lasting ≥ 15 minutes, skull fracture, subdural hematoma, or febrile seizures) or need for therapy with anticonvulsant medication.
  • History of treatment with bupropion or naltrexone within 12 months
  • Positive urine drug screen - STAT test performed on each day of study.
  • Pregnant or breast-feeding
  • Planned surgical procedure or trip that can impact the conduct of the study
  • Use of investigational drug, device or procedure within 30 days
  • Any condition which in the opinion of the investigator makes the subject unsuitable for inclusion in this study
  • Participation in any previous clinical trial sponsored by Orexigen Therapeutics.
  • Study personnel, sponsor representatives and their immediate families.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Placebo tablets
fMRI to assess the effects of the drug/placebo on areas of the brain
Other Names:
  • functional magnetic resonance imaging to assess the effects of the drug/placebo on areas of the brain
Experimental: NB32
Naltrexone SR 32 mg/bupropion SR 360 mg/day
fMRI to assess the effects of the drug/placebo on areas of the brain
Other Names:
  • functional magnetic resonance imaging to assess the effects of the drug/placebo on areas of the brain

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response to Food Related Cues Using Functional Magnetic Resonance Imaging - Superior Frontal
Time Frame: Baseline, 4 weeks
Assessment of differences in brain activation in response to food cues before and after 4 weeks of treatment in subjects receiving NB or placebo.
Baseline, 4 weeks
Response to Food Related Cues Using Functional Magnetic Resonance Imaging - Anterior Cingulate
Time Frame: Baseline, 4 weeks
Assessment of differences in brain activation in response to food cues before and after 4 weeks of treatment in subjects receiving NB or placebo.
Baseline, 4 weeks
Response to Food Related Cues Using Functional Magnetic Resonance Imaging - Hippocampal Region 1
Time Frame: Baseline, 4 weeks
Assessment of differences in brain activation in response to food cues before and after 4 weeks of treatment in subjects receiving NB or placebo.
Baseline, 4 weeks
Response to Food Related Cues Using Functional Magnetic Resonance Imaging - Hippocampal Region 2
Time Frame: Baseline, 4 weeks
Assessment of differences in brain activation in response to food cues before and after 4 weeks of treatment in subjects receiving NB or placebo.
Baseline, 4 weeks
Response to Food Related Cues Using Functional Magnetic Resonance Imaging - Superior Parietal
Time Frame: Baseline, 4 weeks
Assessment of differences in brain activation in response to food cues before and after 4 weeks of treatment in subjects receiving NB or placebo.
Baseline, 4 weeks
Response to Food Related Cues Using Functional Magnetic Resonance Imaging - Posterior Insula
Time Frame: Baseline, 4 weeks
Assessment of differences in brain activation in response to food cues before and after 4 weeks of treatment in subjects receiving NB or placebo.
Baseline, 4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent Change in Body Weight
Time Frame: Baseline, 4 weeks
Baseline, 4 weeks
Dutch Eating Behavior Questionnaire - Change in Restrained Eating Subscale Score
Time Frame: Baseline, 4 weeks
The Dutch Eating Behavior Questionnaire is a 33-item self-report measure designed to assess the type of eating behavior and is organized into 3 subscales (emotional eating, externally-induced eating, and restrained eating). Subjects rated the frequency of their eating behaviors using a 5-point scale, where 1=never, 2=seldom, 3=sometimes, 4=often, and 5=very often. The Restrained Eating subscale consisted of 10 items and the scores ranged from 10 (worse outcome) to 50 (better outcome).
Baseline, 4 weeks
Dutch Eating Behavior Questionnaire - Change in Emotional Eating A Subscale Score
Time Frame: Baseline, 4 weeks
The Dutch Eating Behavior Questionnaire is a 33-item self-report measure designed to assess the type of eating behavior and is organized into 3 subscales (emotional eating, externally-induced eating, and restrained eating). Subjects rated the frequency of their eating behaviors using a 5-point scale, where 1=never, 2=seldom, 3=sometimes, 4=often, and 5=very often. The Emotional Eating A subscale (clearly labeled emotions) consisted of 9 items and the scores ranged from 9 (better outcome) to 45 (worse outcome).
Baseline, 4 weeks
Dutch Eating Behavior Questionnaire - Change in Emotional Eating B Subscale Score
Time Frame: Baseline, 4 weeks
The Dutch Eating Behavior Questionnaire is a 33-item self-report measure designed to assess the type of eating behavior and is organized into 3 subscales (emotional eating, externally-induced eating, and restrained eating). Subjects rated the frequency of their eating behaviors using a 5-point scale, where 1=never, 2=seldom, 3=sometimes, 4=often, and 5=very often. The Emotional Eating B subscale (diffuse emotions) consisted of 4 items and the scores ranged from 4 (better outcome) to 20 (worse outcome).
Baseline, 4 weeks
Dutch Eating Behavior Questionnaire - Change in External Eating Subscale Score
Time Frame: Baseline, 4 weeks
The Dutch Eating Behavior Questionnaire is a 33-item self-report measure designed to assess the type of eating behavior and is organized into 3 subscales (emotional eating, externally-induced eating, and restrained eating). Subjects rated the frequency of their eating behaviors using a 5-point scale where 1=never, 2=seldom, 3=sometimes, 4=often, and 5=very often. The External Eating subscale consisted of 10 items and the scores ranged from 10 (better outcome) to 50 (worse outcome).
Baseline, 4 weeks
Change in Question 19 From 21-Item COE (Control of Eating) Questionnaire
Time Frame: Baseline, 4 weeks
Question 19: Generally, how difficult has it been to control your eating? Scoring: 0=not at all difficult; 100=extremely difficult
Baseline, 4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Gene-Jack Wang, MD, Brookhaven National Laboratory

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2008

Primary Completion (Actual)

June 1, 2010

Study Completion (Actual)

June 1, 2010

Study Registration Dates

First Submitted

July 3, 2008

First Submitted That Met QC Criteria

July 3, 2008

First Posted (Estimate)

July 9, 2008

Study Record Updates

Last Update Posted (Estimate)

January 6, 2015

Last Update Submitted That Met QC Criteria

January 5, 2015

Last Verified

December 1, 2014

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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