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

NCT00711477 | Completed Phase 2 Results

• 1 other identifier: NB-431
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Obesity

Keywords

obesity; overweight; magnetic resonance imaging; naltrexone; bupropion

Outcome Measures

Primary Outcomes (6)

• Response to Food Related Cues Using Functional Magnetic Resonance Imaging - Superior Frontal

  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

  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

  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

  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

  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

  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 Outcomes (6)

• Percent Change in Body Weight

  Baseline, 4 weeks

• Dutch Eating Behavior Questionnaire - Change in Restrained Eating Subscale Score

  Baseline, 4 weeks

• Dutch Eating Behavior Questionnaire - Change in Emotional Eating A Subscale Score

  Baseline, 4 weeks

• Dutch Eating Behavior Questionnaire - Change in Emotional Eating B Subscale Score

  Baseline, 4 weeks

• Dutch Eating Behavior Questionnaire - Change in External Eating Subscale Score

  Baseline, 4 weeks

Study Arms (2)

NB32

EXPERIMENTAL

Naltrexone SR 32 mg/bupropion SR 360 mg/day

Drug: Naltrexone SR 32 mg/bupropion SR 360 mg/day; Other: fMRI scan

Placebo

PLACEBO COMPARATOR

Placebo tablets

Drug: Placebo; Other: fMRI scan

Interventions

Naltrexone SR 32 mg/bupropion SR 360 mg/day DRUG

NB32

Placebo DRUG

Placebo

fMRI scan OTHER

fMRI to assess the effects of the drug/placebo on areas of the brain

Also known as: functional magnetic resonance imaging to assess the effects of the drug/placebo on areas of the brain

NB32; Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Orexigen Therapeutics, Inc: lead

Study Sites (1)

Brookhaven National Laboratory Medical Department

Upton, New York, 11973, United States

Location

Related Publications (1)

• Wang GJ, Tomasi D, Volkow ND, Wang R, Telang F, Caparelli EC, Dunayevich E. Effect of combined naltrexone and bupropion therapy on the brain's reactivity to food cues. Int J Obes (Lond). 2014 May;38(5):682-8. doi: 10.1038/ijo.2013.145. Epub 2013 Aug 8.

  PMID: 23924756 BACKGROUND

MeSH Terms

Conditions

Obesity; Overweight

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Senior Vice President, Head of Global Development
• Organization: Orexigen Therapeutics, Inc.

MedInfo@Orexigen.com

(858) 875-8600

Study Officials

• Gene-Jack Wang, MD

  Brookhaven National Laboratory

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2008
• First Posted: July 9, 2008
• Study Start: September 1, 2008
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2010
• Last Updated: January 6, 2015
• Results First Posted: January 6, 2015

Record last verified: 2014-12

Locations

US (1)