Study of Amantadine for Weight Stabilization During Olanzapine Treatment

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by:
University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT00287352
First received: February 3, 2006
Last updated: April 29, 2011
Last verified: April 2011
  Purpose

Weight gain associated with antipsychotic medication use is a major side effect that limits the tolerability of these drugs. This often significant weight gain adversely affects health, increasing risks for developing cardiovascular disease, diabetes, sleep apnea, cancers of the colon, kidneys, uterus, endometrium and esophagus and osteoarthritis. Beasley and colleagues (1997) reported that 40.5% of olanzapine-treated patients gained more than 7% of baseline weight. Much of the olanzapine induced weight gain occurs early in treatment, and antipsychotic-naïve and young patients (Woods et al., 2002) are particularly vulnerable to this side effect. One of the most promising medications to aid weight loss in patients taking olanzapine is amantadine.

Attempts at preventing weight gain are expected to be more successful than attempts to reverse it once it occurs. It is now common clinical practice to educate all patients beginning treatment with olanzapine, and other antipsychotics, about healthy eating and the need for exercise. However, despite this effort, weight gain in this population continues. Beginning a weight-stabilizing medication after a low threshold of weight gain has occurred may have significant impact on patients' health and their willingness to continue to take antipsychotics.

We propose to investigate the efficacy of amantadine as a weight-stabilizing agent in a population of first-episode psychotic subjects just beginning treatment with antipsychotic agents. This population is generally young and medically healthy, without contraindications to amantadine. They are often of normal body mass index and without obesity-related medical problems. They have much to gain in preventing the weight gain which so often progresses steadily over the course of treatment, is difficult to reverse and results in significant morbidity and mortality. Additionally, the first episode psychotic population tends to take fewer concomitant psychiatric medications. This is important since these medications may cause weight gain (long term use of mirtazapine, lithium, depakote) or weight loss (short term use of SSRI's) which could confound the effectiveness of amantadine to combat weight gain.


Condition Intervention Phase
Psychotic Disorder
Schizophreniform Disorder
Schizophrenia
Schizoaffective Disorder
Mood Disorders With Psychotic Features
Drug: Olanzapine, Amantadine
Drug: Olanzapine and placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Double Blind Placebo Controlled Investigation of Amantadine for Retarding Weight Gain in First Episode Adlt Psychotic Subjects Beginning Therapy With Olanzapine.

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • To compare time to clinical significant weight gain in the amantadine + olanzapine group with the placebo + olanzapine group. [ Time Frame: 29 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • We will determine if the amantadine + olanzapine group has a lower % body fat compared to the placebo + olanzapine group at 16 weeks [ Time Frame: 29 weeks ] [ Designated as safety issue: Yes ]
  • We will determine if the amantadine +olanzapine group has a higher RQ signifying better fat utilization compared to the placebo + olanzapine group at 16 weeks [ Time Frame: 29 weeks ] [ Designated as safety issue: Yes ]
  • We will determine if the amantadine + olanzapine group has significantly better metabolic profile at 16 weeks as compared to the placebo + olanzapine group. [ Time Frame: 29 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 40
Study Start Date: May 2005
Study Completion Date: September 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Double-Blind Treatment
Olanzapine continuing with placebo
Drug: Olanzapine and placebo
Olanzapine continuing as clinically indicated
Active Comparator: Olanzapine, Amantadine
Standard combine with Amantadine
Drug: Olanzapine, Amantadine
Olanzapine continuing as clinically indicated, Amantadine 100 mg tid

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Ages 18-65
  • Male and female
  • DSM IV diagnosis of psychotic episode (brief psychotic disorder, schizophreniform disorder, schizophrenia, schizoaffective disorder)or mood disorder with psychotic features
  • Subjects may have lifetime exposure to antipsychotic medications other than olanzapine of up to 8 weeks
  • Olanzapine monotherapy is appropriate treatment as judged by their treating physician.

Less than 12 weeks of olanzapine monotherapy treatment at entrance into phase 1.

  • Able to consent
  • Female subjects require medically acceptable means of birth control which includes tubal ligation, hysterectomy, condoms, oral contraceptives, IUD, cervical cap, diaphragm, transdermal contraceptive patch, and abstinence.

Exclusion Criteria:

  • Current treatment with lithium, depakote, carbamazepine, lamotrigine, mirtazapine, corticosteroids, or stimulants (methamphetamine, etc).
  • Known sensitivity or contraindication to amantadine
  • Suicidal or homicidal risk
  • Pregnant, desiring to become pregnant during the study period, or lactating
  • Serious or unstable medical illness that require ongoing treatment with medication
  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: NCT00287352

Locations
United States, North Carolina
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27599
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Eli Lilly and Company
Investigators
Principal Investigator: Karen A Graham, MSc MD University of North Carolina, Chapel Hill
  More Information

No publications provided

Responsible Party: Karen A. Graham, Msc, MD/Principal Investigator, University of North Carolina at Chapel Hill
ClinicalTrials.gov Identifier: NCT00287352     History of Changes
Other Study ID Numbers: F1D-MC-X273, GCRC 2235
Study First Received: February 3, 2006
Last Updated: April 29, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by University of North Carolina, Chapel Hill:
First episode psychosis

Additional relevant MeSH terms:
Psychotic Disorders
Mental Disorders
Schizophrenia
Mood Disorders
Schizophrenia and Disorders with Psychotic Features
Amantadine
Olanzapine
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Antiemetics
Autonomic Agents
Gastrointestinal Agents
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Serotonin Uptake Inhibitors

ClinicalTrials.gov processed this record on August 18, 2014