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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Orexigen Therapeutics, Inc
ClinicalTrials.gov Identifier:
NCT00711477
First received: July 3, 2008
Last updated: January 5, 2015
Last verified: December 2014
  Purpose

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.


Condition Intervention Phase
Obesity
Drug: Naltrexone SR 32 mg/bupropion SR 360 mg/day
Drug: Placebo
Other: fMRI scan
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Basic Science
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Orexigen Therapeutics, Inc:

Primary Outcome Measures:
  • Response to Food Related Cues Using Functional Magnetic Resonance Imaging - Superior Frontal [ Time Frame: Baseline, 4 weeks ] [ Designated as safety issue: No ]
    Assessment of differences in brain activation in response to food cues before and after 4 weeks of treatment in subjects receiving NB or placebo.

  • Response to Food Related Cues Using Functional Magnetic Resonance Imaging - Anterior Cingulate [ Time Frame: Baseline, 4 weeks ] [ Designated as safety issue: No ]
    Assessment of differences in brain activation in response to food cues before and after 4 weeks of treatment in subjects receiving NB or placebo.

  • Response to Food Related Cues Using Functional Magnetic Resonance Imaging - Hippocampal Region 1 [ Time Frame: Baseline, 4 weeks ] [ Designated as safety issue: No ]
    Assessment of differences in brain activation in response to food cues before and after 4 weeks of treatment in subjects receiving NB or placebo.

  • Response to Food Related Cues Using Functional Magnetic Resonance Imaging - Hippocampal Region 2 [ Time Frame: Baseline, 4 weeks ] [ Designated as safety issue: No ]
    Assessment of differences in brain activation in response to food cues before and after 4 weeks of treatment in subjects receiving NB or placebo.

  • Response to Food Related Cues Using Functional Magnetic Resonance Imaging - Superior Parietal [ Time Frame: Baseline, 4 weeks ] [ Designated as safety issue: No ]
    Assessment of differences in brain activation in response to food cues before and after 4 weeks of treatment in subjects receiving NB or placebo.

  • Response to Food Related Cues Using Functional Magnetic Resonance Imaging - Posterior Insula [ Time Frame: Baseline, 4 weeks ] [ Designated as safety issue: No ]
    Assessment of differences in brain activation in response to food cues before and after 4 weeks of treatment in subjects receiving NB or placebo.


Secondary Outcome Measures:
  • Percent Change in Body Weight [ Time Frame: Baseline, 4 weeks ] [ Designated as safety issue: No ]
  • Dutch Eating Behavior Questionnaire - Change in Restrained Eating Subscale Score [ Time Frame: Baseline, 4 weeks ] [ Designated as safety issue: No ]
    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).

  • Dutch Eating Behavior Questionnaire - Change in Emotional Eating A Subscale Score [ Time Frame: Baseline, 4 weeks ] [ Designated as safety issue: No ]
    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).

  • Dutch Eating Behavior Questionnaire - Change in Emotional Eating B Subscale Score [ Time Frame: Baseline, 4 weeks ] [ Designated as safety issue: No ]
    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).

  • Dutch Eating Behavior Questionnaire - Change in External Eating Subscale Score [ Time Frame: Baseline, 4 weeks ] [ Designated as safety issue: No ]
    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).

  • Change in Question 19 From 21-Item COE (Control of Eating) Questionnaire [ Time Frame: Baseline, 4 weeks ] [ Designated as safety issue: No ]
    Question 19: Generally, how difficult has it been to control your eating? Scoring: 0=not at all difficult; 100=extremely difficult


Enrollment: 46
Study Start Date: September 2008
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: NB32
Naltrexone SR 32 mg/bupropion SR 360 mg/day
Drug: Naltrexone SR 32 mg/bupropion SR 360 mg/day Other: fMRI scan
fMRI to assess the effects of the drug/placebo on areas of the brain
Other Name: functional magnetic resonance imaging to assess the effects of the drug/placebo on areas of the brain
Placebo Comparator: Placebo
Placebo tablets
Drug: Placebo Other: fMRI scan
fMRI to assess the effects of the drug/placebo on areas of the brain
Other Name: functional magnetic resonance imaging to assess the effects of the drug/placebo on areas of the brain

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00711477

Locations
United States, New York
Brookhaven National Laboratory Medical Department
Upton, New York, United States, 11973
Sponsors and Collaborators
Orexigen Therapeutics, Inc
Investigators
Principal Investigator: Gene-Jack Wang, MD Brookhaven National Laboratory
  More Information

Publications:
Responsible Party: Orexigen Therapeutics, Inc
ClinicalTrials.gov Identifier: NCT00711477     History of Changes
Other Study ID Numbers: NB-431
Study First Received: July 3, 2008
Results First Received: October 8, 2014
Last Updated: January 5, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Orexigen Therapeutics, Inc:
obesity
overweight
magnetic resonance imaging
naltrexone
bupropion

Additional relevant MeSH terms:
Bupropion
Naltrexone
Antidepressive Agents
Antidepressive Agents, Second-Generation
Central Nervous System Agents
Dopamine Agents
Dopamine Uptake Inhibitors
Molecular Mechanisms of Pharmacological Action
Narcotic Antagonists
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on March 03, 2015