Effects of Modafinil on Olanzapine Weight Gain
Information source: Neuropsychiatric Research Institute, Fargo, North Dakota
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Weight Gain
Intervention: Olanzapine plus modafinil (Drug); Olanzapine plus placebo (Drug)
Sponsored by: Neuropsychiatric Research Institute, Fargo, North Dakota
Official(s) and/or principal investigator(s):
James L Roerig, PharmD, Principal Investigator, Affiliation: University of North Dakota
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.
Official title: A Comparison of the Effects of Modafinil on Olanzapine Associated Eating Behaviors in Normal Human Subjects
Study design: Prevention, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Pharmacodynamics Study
Primary outcome: Change in weight
Change in Kilocalories consumed
Change in Epworth sleep scale
Change in Food Craving Inventory
Change in delta ghrelin
Change in delta PYY3-36
Change in satiety ratings
Change in hunger ratings
Adverse effect comparison
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.
Minimum age: 18 Years.
Maximum age: 60 Years.
- 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
- Subjects must be of good general health by history and physical exam.
- 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
- 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
- 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.
Locations and Contacts
Neuropsychiatric Research Institute, Fargo, North Dakota 58103, United States
Neuropsychiatric Research Institute web page
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.
Starting date: July 2006
Ending date: August 2007
Last updated: March 10, 2008