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Study of Amantadine for Weight Stabilization During Olanzapine Treatment

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

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

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, 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 ]

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 ]
  • 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 ]
  • 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 ]

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


Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
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Please refer to this study by its identifier: NCT00287352

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
Principal Investigator: Karen A Graham, MSc MD University of North Carolina, Chapel Hill
  More Information

Responsible Party: Karen A. Graham, Msc, MD/Principal Investigator, University of North Carolina at Chapel Hill 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

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

Additional relevant MeSH terms:
Psychotic Disorders
Mental Disorders
Mood Disorders
Pathologic Processes
Schizophrenia Spectrum and Other Psychotic Disorders
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Antiparkinson Agents
Anti-Dyskinesia Agents
Antiviral Agents
Anti-Infective Agents
Dopamine Agents
Analgesics, Non-Narcotic processed this record on April 25, 2017