Weight GainNCT00636896
Effects of Modafinil on Olanzapine Weight Gain
A study testing Olanzapine plus modafinil in people with Weight Gain, run by Neuropsychiatric Research Institute, Fargo, North Dakota at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Weight Gain
- What is being tested?
- Olanzapine plus modafinil
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2006to Aug 2007
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Neuropsychiatric Research Institute
Fargo, North Dakota, 58103
About this study
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.
Read the 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.
- Conditions
- Weight Gain
- Being tested
- Olanzapine plus modafinil, Olanzapine plus placebo
- Keywords
- weight gain, olanzapine, atypical antipsychotic
- Medical subject headings
- Weight Gain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Olanzapine plus modafinilDrug
Also called Zyprexa, Provigil
Olanzapine 10 mg/d plus modafinil 200 mg/d
Olanzapine plus placeboDrug
Also called Zyprexa, Provigil
Olanzapine 10 mg/d plus placebo
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Olanzapine 10 mg plus modafinil 200 mg Receives: Drug: Olanzapine plus modafinil |
| 2 | Placebo comparator | Olanzapine plus Placebo Receives: Drug: Olanzapine plus placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in weight
Measured: 3 weeks
Secondary outcomes (8)
Change in Kilocalories consumed
Measured: Over 3 weeks
Change in Epworth sleep scale
Measured: 3 weeks
Change in Food Craving Inventory
Measured: 3 weeks
Change in delta ghrelin
Measured: 3 weeks
Change in delta PYY3-36
Measured: 3 weeks
Change in satiety ratings
Measured: 3 weeks
Change in hunger ratings
Measured: 3 weeks
Adverse effect comparison
Measured: 3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2008 (estimated)
- Study startJul 2006
- Primary completionAug 2007
- Study completionAug 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Weight GainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Neuropsychiatric Research Institute, Fargo, North Dakota
- Sponsor type
- University, hospital or other
- Collaborators
- Eli Lilly and Company, University of North Dakota
- Investigators
- James L Roerig, PharmD, Principal investigator, University of North Dakota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00636896
- Sponsor's protocol ID
- FID-US-X297
- Status last verified
- Mar 2008
- First submitted
- 10 Mar 2008
- Last updated
- 17 Mar 2008
- Results posted
- No
- Data monitoring committee
- No
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.
PubMed 18204336Roerig 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. doi: 10.1097/01.jcp.0000177549.36585.29.
PubMed 16160615
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Comparison of the Effects of Modafinil on Olanzapine Associated Eating Behaviors in Normal Human Subjects
- ClinicalTrials.gov ID
- NCT00636896
- Acronym / sponsor ID
- FID-US-X297
- Conditions
- Weight Gain
- Keywords
- weight gain, olanzapine, atypical antipsychotic
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Neuropsychiatric Research Institute, Fargo, North DakotaUniversity, hospital or other
- Collaborators
- Eli Lilly and Company, University of North Dakota
- Study start
- Jul 2006
- Primary completion
- Aug 2007 (actual)
- Study completion
- Aug 2007 (actual)
- First posted
- 17 Mar 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Olanzapine plus modafinilOlanzapine 10 mg plus modafinil 200 mg |
| 2 | Placebo comparator | Drug: Olanzapine plus placeboOlanzapine plus Placebo |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Olanzapine plus modafinilAlso: Zyprexa, ProvigilOlanzapine 10 mg/d plus modafinil 200 mg/d | Drug | 1 |
| Olanzapine plus placeboAlso: Zyprexa, ProvigilOlanzapine 10 mg/d plus placebo | Drug | 2 |
Primary outcome
Change in weight
Time frame: 3 weeks
8 secondary outcomes
Change in Kilocalories consumed
Time frame: Over 3 weeks
Change in Epworth sleep scale
Time frame: 3 weeks
Change in Food Craving Inventory
Time frame: 3 weeks
Change in delta ghrelin
Time frame: 3 weeks
Change in delta PYY3-36
Time frame: 3 weeks
Change in satiety ratings
Time frame: 3 weeks
Change in hunger ratings
Time frame: 3 weeks
Adverse effect comparison
Time frame: 3 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2008.
- Background: PubMed 18204336Roerig 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.
- Background: PubMed 16160615Roerig 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. doi: 10.1097/01.jcp.0000177549.36585.29.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James L Roerig, PharmD principal investigator
University of North Dakota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Olanzapine plus modafinil in people with Weight Gain, run by Neuropsychiatric Research Institute, Fargo, North Dakota at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in weight (time frame: 3 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00636896, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2008.