Study of Amantadine for Weight Stabilization During Olanzapine Treatment

NCT00287352 | Completed Phase 1 DMC

• 2 other identifiers: F1D-MC-X273GCRC 2235
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Psychotic Disorder; Schizophreniform Disorder; Schizophrenia; Schizoaffective Disorder; Mood Disorders With Psychotic Features

Keywords

First episode psychosis

Outcome Measures

Primary Outcomes (1)

• To compare time to clinical significant weight gain in the amantadine + olanzapine group with the placebo + olanzapine group.

  29 weeks

Secondary Outcomes (3)

• We will determine if the amantadine + olanzapine group has a lower % body fat compared to the placebo + olanzapine group at 16 weeks

  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

  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.

  29 weeks

Study Arms (2)

Double-Blind Treatment

PLACEBO COMPARATOR

Olanzapine continuing with placebo

Drug: Olanzapine and placebo

Olanzapine, Amantadine

ACTIVE COMPARATOR

Standard combine with Amantadine

Drug: Olanzapine, Amantadine

Interventions

Olanzapine, Amantadine DRUG

Olanzapine continuing as clinically indicated, Amantadine 100 mg tid

Olanzapine, Amantadine

Olanzapine and placebo DRUG

Olanzapine continuing as clinically indicated

Double-Blind Treatment

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• Eli Lilly and Company: collaborator

Study Sites (1)

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

MeSH Terms

Conditions

Psychotic Disorders; Schizophrenia

Interventions

Olanzapine; Amantadine

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Karen A Graham, MSc MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: February 3, 2006
• First Posted: February 6, 2006
• Study Start: May 1, 2005
• Primary Completion: September 1, 2009
• Study Completion: September 1, 2009
• Last Updated: May 2, 2011

Record last verified: 2011-04

Locations

US (1)