Official Title: “A Comparison of the Effects of Modafinil on Olanzapine Associated Eating Behaviors in Normal Human Subjects”

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.

Study Type: Interventional

Study Design: Prevention, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Pharmacodynamics Study

Study Primary Completion Date: August 2007

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.

Intervention(s) in this Clinical Trial

• Drug: Olanzapine plus modafinil
  • Olanzapine 10 mg/d plus modafinil 200 mg/d
• Drug: Olanzapine plus placebo
  • Olanzapine 10 mg/d plus placebo

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Olanzapine 10 mg plus modafinil 200 mg
• Placebo Comparator: 2
  • Olanzapine plus Placebo

Primary Measures

• Change in weight
  • Time Frame: 3 weeks
    Safety Issue?: No

Secondary Measures

• Change in Kilocalories consumed
  • Time Frame: Over 3 weeks
    Safety Issue?: No
• Change in Epworth sleep scale
  • Time Frame: 3 weeks
    Safety Issue?: No
• Change in Food Craving Inventory
  • Time Frame: 3 weeks
    Safety Issue?: No
• Change in delta ghrelin
  • Time Frame: 3 weeks
    Safety Issue?: No
• Change in delta PYY3-36
  • Time Frame: 3 weeks
    Safety Issue?: No
• Change in satiety ratings
  • Time Frame: 3 weeks
    Safety Issue?: No
• Change in hunger ratings
  • Time Frame: 3 weeks
    Safety Issue?: No
• Adverse effect comparison
  • Time Frame: 3 weeks
    Safety Issue?: Yes

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 60 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Neuropsychiatric Research Institute, Fargo, North Dakota

Overall Clinical Trial Officials and Contacts

James L Roerig, PharmD Principal Investigator University of North Dakota  

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00636896

Study ID Number: FID-US-X297

ClinicalTrials.gov Identifier: NCT00636896

Health Authority: United States: Institutional Review Board

Neuropsychiatric Research Institute web page