Effects of Modafinil on Olanzapine Weight Gain - Full Text View

Sponsor:	Neuropsychiatric Research Institute, Fargo, North Dakota
Collaborators:	Eli Lilly and Company University of North Dakota
Information provided by:	Neuropsychiatric Research Institute, Fargo, North Dakota
ClinicalTrials.gov Identifier:	NCT00636896

Purpose

This study is designed as a 3 week, randomized, double blind, placebo controlled, trial. Olanzapine and modafinil will be titrated to 10mg and 200mg respectively. Feeding lab assessments will be conducted at baseline and endpoint. Assessments of hunger/satiety, kilocalories consumed and weight will be obtained. Plasma ghrelin and PYY3-36 levels will be drawn at baseline and endpoint prior to breakfast and two hours post.

Study hypothesis: The modafinil/olanzapine group will gain less weight than the olanzapine/placebo group over three weeks of drug intake.

Condition	Intervention
Weight Gain	Drug: Olanzapine plus modafinil Drug: Olanzapine plus placebo

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Pharmacodynamics Study
Official Title:	A Comparison of the Effects of Modafinil on Olanzapine Associated Eating Behaviors in Normal Human Subjects

Resource links provided by NLM:

Drug Information available for: Modafinil Olanzapine

U.S. FDA Resources

Further study details as provided by Neuropsychiatric Research Institute, Fargo, North Dakota:

Primary Outcome Measures:

Change in weight [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change in Kilocalories consumed [ Time Frame: Over 3 weeks ] [ Designated as safety issue: No ]
Change in Epworth sleep scale [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
Change in Food Craving Inventory [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
Change in delta ghrelin [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
Change in delta PYY3-36 [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
Change in satiety ratings [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
Change in hunger ratings [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
Adverse effect comparison [ Time Frame: 3 weeks ] [ Designated as safety issue: Yes ]

Enrollment:	50
Study Start Date:	July 2006
Study Completion Date:	August 2007
Primary Completion Date:	August 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Olanzapine 10 mg plus modafinil 200 mg	Drug: Olanzapine plus modafinil Olanzapine 10 mg/d plus modafinil 200 mg/d
2: Placebo Comparator Olanzapine plus Placebo	Drug: Olanzapine plus placebo Olanzapine 10 mg/d plus placebo

Detailed Description:

Atypical antipsychotics have become the drugs of choice in the treatment of schizophrenia as well as acute and maintenance therapy for bipolar disorder. In addition, affective disorders have been found to benefit from these agents (Masan 2004). These disorders represent chronic conditions that require extended treatment for years if not lifetimes. In light of the ever widening use of the atypicals, attention must now be focused on adverse reactions that may limit compliance with these agents. Weight gain and sedation have proven to be associated with many atypicals (Allison et al. 1999; Wirshing et al. 1999) including clozapine, olanzapine, risperidone and quetiapine. These side effects can reduce compliance and have detrimental effects on patient's health over long term treatment.

In our previous study, olanzapine and risperidone were demonstrated to affect eating behaviors and weight/BMI compared to placebo in a 2 week paradigm in normal healthy human subjects. Behaviors affected included appetite, reported calories consumed per day, and observed calories consumed in a feeding laboratory. No effects were seen on resting energy expenditure corrected for lean body weight. Also, sedation was reported in 81.3 and 75 % of the olanzapine and risperidone groups respectively. Sedation was the primary reason, in both groups, for medication dose reductions.

Weight gain and sedation have been postulated to be associated with the blockade of central nervous system (CNS) histamine-1 receptors (H1) by the atypical agents (Heisler 1998; Wirshing et al. 1999). In light of this postulated mechanism, it is reasonable to assume that overcoming the H1 blockade with a histamine agonist may aid in reducing these side effects to a tolerable level. Thus, the following study is proposed.

This study is designed as a randomized double blind, parallel group trial to evaluate the effect of modafinil (a proposed H1 agonist) vs. placebo on eating parameters, weight/BMI and sedation in healthy human subjects receiving olanzapine over a three week study period. This project utilizes the current state of the art feeding lab procedures, as reviewed by Mitchell and colleagues (Mitchell et al. 1998), to better characterize the effect of modafinil on olanzapine associated eating behavior. This project will help to determine the efficacy of utilizing a H1 agonist as an adjunctive medication in patients receiving atypical antipsychotic therapy to prevent weight gain and excess sedation.

Eligibility

Ages Eligible for Study:	18 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Male or female subjects between the ages of 18 and 60 years.
Women of child bearing potential must be practicing an accepted method of birth control (barrier method or oral contraceptive) and have a negative pregnancy test at baseline.
Subjects must be of good general health by history and physical exam.

Exclusion Criteria:

Subjects who are allergic to olanzapine or modafinil.
Subjects with a history of a neuroleptic malignant syndrome.
Subjects who have a body mass index at visit 2 less than 20 kg/m2 or greater than 27 kg/m2.
Subjects who are restrictive eaters according to the restraint subscale of the Eating Disorder Evaluation (EDE).
Women who are pregnant or nursing at the time of the study.
Subjects who are lactose intolerant.
Subjects with diabetes mellitus.
Subjects experiencing clinically significant, unstable neurological, cardiac (including cardiac conduction defects), hepatic, renal disease or narrow angle glaucoma.
Subjects diagnosed with anorexia nervosa, bulimia nervosa, or binge eating disorder.
Subjects currently or with a past history of meeting DSM-IV diagnostic criteria for schizophrenia, schizoaffective disorder, bipolar disorder or substance abuse.
Subjects who have participated in an investigational drug study in past 30 days.
Subjects who are receiving any prescription medications other than oral contraceptives that would interact with the study medication or influence appetite or weight.
Subjects who smoke or use any nicotine products.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00636896

Locations

United States, North Dakota
Neuropsychiatric Research Institute
Fargo, North Dakota, United States, 58103

Sponsors and Collaborators

Neuropsychiatric Research Institute, Fargo, North Dakota

Eli Lilly and Company

University of North Dakota

Investigators

Principal Investigator:

James L Roerig, PharmD

University of North Dakota

More Information

Additional Information:

Neuropsychiatric Research Institute web page This link exits the ClinicalTrials.gov site

Publications:

Roerig JL, Steffen KJ, Mitchell JE, Crosby RD, Gosnell BA. A comparison of the effects of olanzapine and risperidone versus placebo on ghrelin plasma levels. J Clin Psychopharmacol. 2008 Feb;28(1):21-6.

Roerig JL, Mitchell JE, de Zwaan M, Crosby RD, Gosnell BA, Steffen KJ, Wonderlich SA. A comparison of the effects of olanzapine and risperidone versus placebo on eating behaviors. J Clin Psychopharmacol. 2005 Oct;25(5):413-8.

Responsible Party:	University of North Dakota ( James L. Roerig Pharm.D. Principal Investigator )
Study ID Numbers:	FID-US-X297
Study First Received:	March 10, 2008
Last Updated:	March 10, 2008
ClinicalTrials.gov Identifier:	NCT00636896 History of Changes
Health Authority:	United States: Institutional Review Board; United States: Food and Drug Administration

Keywords provided by Neuropsychiatric Research Institute, Fargo, North Dakota:

weight gain
olanzapine
atypical antipsychotic

Additional relevant MeSH terms:

Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Olanzapine
Psychotropic Drugs
Antiemetics
Neuroprotective Agents
Modafinil
Body Weight
Signs and Symptoms
Therapeutic Uses
Body Weight Changes

Tranquilizing Agents
Gastrointestinal Agents
Central Nervous System Depressants
Central Nervous System Stimulants
Weight Gain
Antipsychotic Agents
Protective Agents
Serotonin Uptake Inhibitors
Pharmacologic Actions
Serotonin Agents
Autonomic Agents
Peripheral Nervous System Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on November 27, 2009