Effects of Modafinil on Olanzapine Weight Gain
Information source: Neuropsychiatric Research Institute, Fargo, North Dakota
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Weight Gain
Intervention: Olanzapine plus modafinil (Drug); Olanzapine plus placebo (Drug)
Phase: N/A
Status: Completed
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
Summary
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.
Clinical Details
Official title: A Comparison of the Effects of Modafinil on Olanzapine Associated Eating Behaviors in Normal Human Subjects
Study design: Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Prevention
Primary outcome: Change in weight
Secondary outcome: Change in Kilocalories consumedChange 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
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
Minimum age: 18 Years.
Maximum age: 60 Years.
Gender(s): Both.
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.
Locations and Contacts
Neuropsychiatric Research Institute, Fargo, North Dakota 58103, United States
Additional Information
Neuropsychiatric Research Institute web page
Related 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. doi: 10.1097/jcp.0b013e3181613325. 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
Last updated: March 10, 2008
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