Psychotic DisorderPhase 1NCT00287352
Study of Amantadine for Weight Stabilization During Olanzapine Treatment
A Phase 1 study testing Olanzapine, Amantadine in people with Psychotic Disorder and Schizophreniform Disorder, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial summary
Weight gain associated with antipsychotic medication use is a major side effect that limits the tolerability of these drugs. This often significant weight gain adversely affects health, increasing risks for developing cardiovascular disease, diabetes, sleep apnea, cancers of the colon, kidneys, uterus, endometrium and… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Psychotic Disorder, Schizophreniform Disorder, Schizophrenia
- What is being tested?
- Olanzapine, Amantadine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- May 2005to Sep 2009
- Phase
- Phase 1
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ages 18-65
- Male and female
- DSM IV diagnosis of psychotic episode (brief psychotic disorder, schizophreniform disorder, schizophrenia, schizoaffective disorder)or mood disorder with psychotic features
- Subjects may have lifetime exposure to antipsychotic medications other than olanzapine of up to 8 weeks
- Olanzapine monotherapy is appropriate treatment as judged by their treating physician.
- Less than 12 weeks of olanzapine monotherapy treatment at entrance into phase 1.
- Able to consent
- Female subjects require medically acceptable means of birth control which includes tubal ligation, hysterectomy, condoms, oral contraceptives, IUD, cervical cap, diaphragm, transdermal contraceptive patch, and abstinence.
Who cannot join
- Current treatment with lithium, depakote, carbamazepine, lamotrigine, mirtazapine, corticosteroids, or stimulants (methamphetamine, etc).
- Known sensitivity or contraindication to amantadine
- Suicidal or homicidal risk
- Pregnant, desiring to become pregnant during the study period, or lactating
- Serious or unstable medical illness that require ongoing treatment with medication
Trial locations and contacts
1 site in 1 country.
United States1 site
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
About this study
Official title: Double Blind Placebo Controlled Investigation of Amantadine for Retarding Weight Gain in First Episode Adlt Psychotic Subjects Beginning Therapy With Olanzapine.
Weight gain associated with antipsychotic medication use is a major side effect that limits the tolerability of these drugs. This often significant weight gain adversely affects health, increasing risks for developing cardiovascular disease, diabetes, sleep apnea, cancers of the colon, kidneys, uterus, endometrium and esophagus and osteoarthritis. Beasley and colleagues (1997) reported that 40.5% of olanzapine-treated patients gained more than 7% of baseline weight. Much of the olanzapine induced weight gain occurs early in treatment, and antipsychotic-naïve and young patients (Woods et al., 2002) are particularly vulnerable to this side effect. One of the most promising medications to aid weight loss in patients taking olanzapine is amantadine.
Attempts at preventing weight gain are expected to be more successful than attempts to reverse it once it occurs. It is now common clinical practice to educate all patients beginning treatment with olanzapine, and other antipsychotics, about healthy eating and the need for exercise. However, despite this effort, weight gain in this population continues. Beginning a weight-stabilizing medication after a low threshold of weight gain has occurred may have significant impact on patients' health and their willingness to continue to take antipsychotics.
We propose to investigate the efficacy of amantadine as a weight-stabilizing agent in a population of first-episode psychotic subjects just beginning treatment with antipsychotic agents. This population is generally young and medically healthy, without contraindications to amantadine. They are often of normal body mass index and without obesity-related medical problems. They have much to gain in preventing the weight gain which so often progresses steadily over the course of treatment, is difficult to reverse and results in significant morbidity and mortality. Additionally, the first episode psychotic population tends to take fewer concomitant psychiatric medications. This is important since these medications may cause weight gain (long term use of mirtazapine, lithium, depakote) or weight loss (short term use of SSRI's) which could confound the effectiveness of amantadine to combat weight gain.
Read the detailed description
Screening: Screening will include demographics, medical and psychiatric histories and a clinical interview to determine psychiatric diagnosis. Screening will also include a physical examination and laboratory assessments (CBC, electrolytes, kidney function, liver function, TSH) to rule out concurrent medical illness that could be a contraindication to amantadine treatment. Blood will also be drawn for fasting lipid profile, glucose, insulin, C reactive protein, adiponectin, and leptin. Subjects will also have the option of allowing us to draw 2 additional tubes for as yet to be determined studies, not to include HIV or genetic testing. Subjects will also have the option of allowing us to draw 1 additional tube for platelet-specific protein assay, termed SEPT5. The rationale for measuring SEPT5 levels is to test a hypothesis that individuals with clinically-defined mental disorders have altered levels of this protein in their circulating blood platelets. A urine drug screen will be performed.
Phase 1: Subjects may enter Phase 1 within the first 12 weeks of treatment with olanzapine. At entry into Phase 1, anthropometric measurements will be taken (height, weight, waist and hip circumference) and BMI calculated. Baseline assessments will include questionnaires about hunger (to be done in the fasting state) (Subjective Satiety Scale), and activity (Baeckea Activity Questionnaire), respiratory quotient (RQ) and resting energy expenditure (REE) assessed using the Medgraphics metabolic cart, and body composition determined by dual x-ray absorptiometry (DXA, Hologic Delphia). Prior to every DXA scan Body Composition Lab personnel will administer a safety questionnaire and women of reproductive age will have a blood pregnancy test. Visits will be scheduled weekly to monitor weight and to provide healthy lifestyle counseling based on the Solutions for Wellness program developed by Lilly. During the first 3 weeks, subjects will be called by research personnel once per week to complete a 24 hour diet recall by phone. During the first 4 weeks of the study, RQ and capillary glucose will be repeated weekly since it is anticipated that changes to these parameters may occur early on. At monthly intervals clinical interviews will monitor for changes in psychosis and blood pressure will be assessed. When subjects gain 1 BMI unit, fasting bloodwork and baseline assessments are repeated and they are enrolled in Phase 2. Subjects who do not gain 1 BMI unit within 12 weeks of olanzapine treatment will end study participation at the end of Phase 1.
Phase 2: Subjects may enter Phase 2 following Phase 1 or enter directly if there is documentation of more than 1 but less than 3 BMI units of weight gain and they have started olanzapine within the previous 12 weeks. Phase 2 is a double blind placebo controlled addition of amantadine to ongoing olanzapine therapy. All subjects entering Phase 2 will have anthropometric measurements, and BMI will be calculated. Fasting lipid profile, glucose, insulin, C reactive protein, adiponectin, and leptin will be obtained, as will liver function tests and a urine drug screen. Body composition by DXA as well as RQ and REE will be determined. Prior to every DXA scan the Body Composition Lab will administer a safety questionnaire and women of reproductive age will have a pregnancy test. A Food Propensity questionnaire will be administered to document recent trends in food choices, and the exercise and hunger questionnaires will also been done. Following completion of baseline assessments, randomization to amantadine or placebo will occur. Subjects will begin taking 1 capsule daily for 2 days, 2 capsules daily for 5 days, and then 3 capsules daily. Amantadine capsules will each contain 100 mg of amantadine. Clinical state and emergence of side effects, including orthostatic hypotension, will be monitored at all visits by research clinicians. If subjects experience mild side effects with increase in number of capsules, the titration will be slowed. During Phase 2, subjects will be called by research personnel on 3 nonconsecutive days to complete a 24 hour diet recall by phone. Biweekly, all subjects will meet with a study physician or nurse for standardized healthy lifestyle counseling based on the Solutions for Wellness program available from Lilly. BMI will be calculated biweekly and baseline measures will be repeated at the final study visit. Urine pregnancy test will be performed monthly on all women. When subjects gain an additional 3 BMI units (approximately 15 lbs), or when they complete 16 weeks of double blind medication they will repeat all Visit 13 measures and end study participation.
- Conditions
- Psychotic Disorder, Schizophreniform Disorder, Schizophrenia, Schizoaffective Disorder, Mood Disorders With Psychotic Features
- Being tested
- Olanzapine, Amantadine, Olanzapine and placebo
- Keywords
- First episode psychosis
- Medical subject headings
- Psychotic Disorders, Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Olanzapine, AmantadineDrug
Olanzapine continuing as clinically indicated, Amantadine 100 mg tid
Olanzapine and placeboDrug
Olanzapine continuing as clinically indicated
| Study group | Role | What they receive |
|---|---|---|
| Double-Blind Treatment | Placebo comparator | Olanzapine continuing with placebo Receives: Drug: Olanzapine and placebo |
| Olanzapine, Amantadine | Active comparator | Standard combine with Amantadine Receives: Drug: Olanzapine, Amantadine |
What is being measured
The primary outcome is the main question the study is designed to answer.
To compare time to clinical significant weight gain in the amantadine + olanzapine group with the placebo + olanzapine group.
Measured: 29 weeks
Secondary outcomes (3)
We will determine if the amantadine + olanzapine group has a lower % body fat compared to the placebo + olanzapine group at 16 weeks
Measured: 29 weeks
We will determine if the amantadine +olanzapine group has a higher RQ signifying better fat utilization compared to the placebo + olanzapine group at 16 weeks
Measured: 29 weeks
We will determine if the amantadine + olanzapine group has significantly better metabolic profile at 16 weeks as compared to the placebo + olanzapine group.
Measured: 29 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2006 (estimated)
- Study startMay 2005
- Primary completionSep 2009
- Study completionSep 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Psychotic DisorderStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- Eli Lilly and Company
- Investigators
- Karen A Graham, MSc MD, Principal investigator, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00287352
- Sponsor's protocol ID
- F1D-MC-X273
- Other IDs
- GCRC 2235
- Status last verified
- Apr 2011
- First submitted
- 3 Feb 2006
- Last updated
- 2 May 2011
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 May 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double Blind Placebo Controlled Investigation of Amantadine for Retarding Weight Gain in First Episode Adlt Psychotic Subjects Beginning Therapy With Olanzapine.
- ClinicalTrials.gov ID
- NCT00287352
- Acronym / sponsor ID
- F1D-MC-X273
- Conditions
- Psychotic Disorder, Schizophreniform Disorder, Schizophrenia, Schizoaffective Disorder, Mood Disorders With Psychotic Features
- Keywords
- First episode psychosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- Eli Lilly and Company
- Study start
- May 2005
- Primary completion
- Sep 2009 (actual)
- Study completion
- Sep 2009 (actual)
- First posted
- 6 Feb 2006 (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.
Weight gain associated with antipsychotic medication use is a major side effect that limits the tolerability of these drugs. This often significant weight gain adversely affects health, increasing risks for developing cardiovascular disease, diabetes, sleep apnea, cancers of the colon, kidneys, uterus, endometrium and esophagus and osteoarthritis. Beasley and colleagues (1997) reported that 40.5% of olanzapine-treated patients gained more than 7% of baseline weight. Much of the olanzapine induced weight gain occurs early in treatment, and antipsychotic-naïve and young patients (Woods et al., 2002) are particularly vulnerable to this side effect. One of the most promising medications to aid weight loss in patients taking olanzapine is amantadine.
Attempts at preventing weight gain are expected to be more successful than attempts to reverse it once it occurs. It is now common clinical practice to educate all patients beginning treatment with olanzapine, and other antipsychotics, about healthy eating and the need for exercise. However, despite this effort, weight gain in this population continues. Beginning a weight-stabilizing medication after a low threshold of weight gain has occurred may have significant impact on patients' health and their willingness to continue to take antipsychotics.
We propose to investigate the efficacy of amantadine as a weight-stabilizing agent in a population of first-episode psychotic subjects just beginning treatment with antipsychotic agents. This population is generally young and medically healthy, without contraindications to amantadine. They are often of normal body mass index and without obesity-related medical problems. They have much to gain in preventing the weight gain which so often progresses steadily over the course of treatment, is difficult to reverse and results in significant morbidity and mortality. Additionally, the first episode psychotic population tends to take fewer concomitant psychiatric medications. This is important since these medications may cause weight gain (long term use of mirtazapine, lithium, depakote) or weight loss (short term use of SSRI's) which could confound the effectiveness of amantadine to combat weight gain.
Detailed description
Screening: Screening will include demographics, medical and psychiatric histories and a clinical interview to determine psychiatric diagnosis. Screening will also include a physical examination and laboratory assessments (CBC, electrolytes, kidney function, liver function, TSH) to rule out concurrent medical illness that could be a contraindication to amantadine treatment. Blood will also be drawn for fasting lipid profile, glucose, insulin, C reactive protein, adiponectin, and leptin. Subjects will also have the option of allowing us to draw 2 additional tubes for as yet to be determined studies, not to include HIV or genetic testing. Subjects will also have the option of allowing us to draw 1 additional tube for platelet-specific protein assay, termed SEPT5. The rationale for measuring SEPT5 levels is to test a hypothesis that individuals with clinically-defined mental disorders have altered levels of this protein in their circulating blood platelets. A urine drug screen will be performed.
Phase 1: Subjects may enter Phase 1 within the first 12 weeks of treatment with olanzapine. At entry into Phase 1, anthropometric measurements will be taken (height, weight, waist and hip circumference) and BMI calculated. Baseline assessments will include questionnaires about hunger (to be done in the fasting state) (Subjective Satiety Scale), and activity (Baeckea Activity Questionnaire), respiratory quotient (RQ) and resting energy expenditure (REE) assessed using the Medgraphics metabolic cart, and body composition determined by dual x-ray absorptiometry (DXA, Hologic Delphia). Prior to every DXA scan Body Composition Lab personnel will administer a safety questionnaire and women of reproductive age will have a blood pregnancy test. Visits will be scheduled weekly to monitor weight and to provide healthy lifestyle counseling based on the Solutions for Wellness program developed by Lilly. During the first 3 weeks, subjects will be called by research personnel once per week to complete a 24 hour diet recall by phone. During the first 4 weeks of the study, RQ and capillary glucose will be repeated weekly since it is anticipated that changes to these parameters may occur early on. At monthly intervals clinical interviews will monitor for changes in psychosis and blood pressure will be assessed. When subjects gain 1 BMI unit, fasting bloodwork and baseline assessments are repeated and they are enrolled in Phase 2. Subjects who do not gain 1 BMI unit within 12 weeks of olanzapine treatment will end study participation at the end of Phase 1.
Phase 2: Subjects may enter Phase 2 following Phase 1 or enter directly if there is documentation of more than 1 but less than 3 BMI units of weight gain and they have started olanzapine within the previous 12 weeks. Phase 2 is a double blind placebo controlled addition of amantadine to ongoing olanzapine therapy. All subjects entering Phase 2 will have anthropometric measurements, and BMI will be calculated. Fasting lipid profile, glucose, insulin, C reactive protein, adiponectin, and leptin will be obtained, as will liver function tests and a urine drug screen. Body composition by DXA as well as RQ and REE will be determined. Prior to every DXA scan the Body Composition Lab will administer a safety questionnaire and women of reproductive age will have a pregnancy test. A Food Propensity questionnaire will be administered to document recent trends in food choices, and the exercise and hunger questionnaires will also been done. Following completion of baseline assessments, randomization to amantadine or placebo will occur. Subjects will begin taking 1 capsule daily for 2 days, 2 capsules daily for 5 days, and then 3 capsules daily. Amantadine capsules will each contain 100 mg of amantadine. Clinical state and emergence of side effects, including orthostatic hypotension, will be monitored at all visits by research clinicians. If subjects experience mild side effects with increase in number of capsules, the titration will be slowed. During Phase 2, subjects will be called by research personnel on 3 nonconsecutive days to complete a 24 hour diet recall by phone. Biweekly, all subjects will meet with a study physician or nurse for standardized healthy lifestyle counseling based on the Solutions for Wellness program available from Lilly. BMI will be calculated biweekly and baseline measures will be repeated at the final study visit. Urine pregnancy test will be performed monthly on all women. When subjects gain an additional 3 BMI units (approximately 15 lbs), or when they complete 16 weeks of double blind medication they will repeat all Visit 13 measures and end study participation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Double-Blind Treatment | Placebo comparator | Drug: Olanzapine and placeboOlanzapine continuing with placebo |
| Olanzapine, Amantadine | Active comparator | Drug: Olanzapine, AmantadineStandard combine with Amantadine |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Ages 18-65
- Male and female
- DSM IV diagnosis of psychotic episode (brief psychotic disorder, schizophreniform disorder, schizophrenia, schizoaffective disorder)or mood disorder with psychotic features
- Subjects may have lifetime exposure to antipsychotic medications other than olanzapine of up to 8 weeks
- Olanzapine monotherapy is appropriate treatment as judged by their treating physician.
Key exclusion criteria (5 listed)
- Current treatment with lithium, depakote, carbamazepine, lamotrigine, mirtazapine, corticosteroids, or stimulants (methamphetamine, etc).
- Known sensitivity or contraindication to amantadine
- Suicidal or homicidal risk
- Pregnant, desiring to become pregnant during the study period, or lactating
- Serious or unstable medical illness that require ongoing treatment with medication
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, AmantadineOlanzapine continuing as clinically indicated, Amantadine 100 mg tid | Drug | Olanzapine, Amantadine |
| Olanzapine and placeboOlanzapine continuing as clinically indicated | Drug | Double-Blind Treatment |
Primary outcome
To compare time to clinical significant weight gain in the amantadine + olanzapine group with the placebo + olanzapine group.
Time frame: 29 weeks
3 secondary outcomes
We will determine if the amantadine + olanzapine group has a lower % body fat compared to the placebo + olanzapine group at 16 weeks
Time frame: 29 weeks
We will determine if the amantadine +olanzapine group has a higher RQ signifying better fat utilization compared to the placebo + olanzapine group at 16 weeks
Time frame: 29 weeks
We will determine if the amantadine + olanzapine group has significantly better metabolic profile at 16 weeks as compared to the placebo + olanzapine group.
Time frame: 29 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 2 May 2011.
Related trials for Psychotic Disorder
RecruitingPhase 3
A Study to Evaluate the Long-term Safety and Tolerability of Xanomeline and Trospium Chloride for the Treatment of Psychiatric Disorders in Children and Adolescents
Schizophrenia, Autism-Related Irritability
Not yet recruitingObservational study
Sleep Monitoring for Early Detection of Relapse in People With Schizophrenia or Bipolar Disorder Receiving Usual Treatment
Bipolar Disorder (BD), SCHIZOPHRENIA 1 (Disorder)
Not yet recruitingPhase 1
Pharmacokinetics and Relative Bioavailability of Intranasal vs Intramuscular Olanzapine in Healthy Adult Participants
Healthy Adult Participants
Active, not recruiting
Designing and Evaluating a Classroom-Based Mental Health Programme for Adolescents.
Mental Health Promotion
RecruitingPhase 2/3
ACP-204 in Adults With Alzheimer's Disease Psychosis
Alzheimer's Disease Psychosis
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.
Karen A Graham, MSc MD principal investigator
University of North Carolina, Chapel Hill
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Olanzapine, Amantadine in people with Psychotic Disorder and Schizophreniform Disorder, run by University of North Carolina, Chapel Hill 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 8 inclusion and 5 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 2 May 2011. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
To compare time to clinical significant weight gain in the amantadine + olanzapine group with the placebo + olanzapine group. (time frame: 29 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 May 2011.