Effects of Modafinil on Olanzapine Weight Gain
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 Design:||Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||A Comparison of the Effects of Modafinil on Olanzapine Associated Eating Behaviors in Normal Human Subjects|
- Change in weight [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
- 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 ]
|Study Start Date:||July 2006|
|Study Completion Date:||August 2007|
|Primary Completion Date:||August 2007 (Final data collection date for primary outcome measure)|
Olanzapine 10 mg plus modafinil 200 mg
Drug: Olanzapine plus modafinil
Olanzapine 10 mg/d plus modafinil 200 mg/d
Placebo Comparator: 2
Olanzapine plus Placebo
Drug: Olanzapine plus placebo
Olanzapine 10 mg/d plus placebo
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00636896
|United States, North Dakota|
|Neuropsychiatric Research Institute|
|Fargo, North Dakota, United States, 58103|
|Principal Investigator:||James L Roerig, PharmD||University of North Dakota|