SchizophreniaNCT00815854
Examining Risk Factors for Atypical Antipsychotic Metabolic Side Effects
A study testing Folic Acid in people with Schizophrenia, run by University of Michigan at 1 site in United States.
Trial summary
This study will examine possible causes of metabolic side effects in people taking atypical antipsychotic (AAP) medications. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Folic Acid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 88 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2008to May 2019
- 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 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- DSM-IV diagnosis of schizophrenia, schizophreniform disorder, schizoaffective disorder, or psychosis not otherwise specified
- Treatment with one of the following atypical antipsychotics (AAPs) for at least 6 months: clozapine, olanzapine, risperidone, quetiapine, aripiprazole, or ziprasidone
- Previous participation in Phase 1 pharmacogenomic study
- Meets metabolic syndrome criteria
- No medication changes for 6 months, including antipsychotic medication changes and changes in any other medications related to treating metabolic syndrome, diabetes, hypertension, or hyperlipidemia
- At least 18 years old and presence of a DSM-IV diagnosis of schizophrenia, schizophreniform disorder, schizoaffective disorder, or psychosis NOS
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- Receiving atypical antipsychotic medication for at least 6 months
- Currently meet ≥ 2 of the NCEP-ATP-III criteria for metabolic syndrome
- No medication changes within the last two months
- Vitamin B12 levels within normal laboratory levels
- No illicit drug use in the past month
Who cannot join
- Presence of any serious medical condition that would significantly affect weight changes, such as neoplastic or thyroid disease
- Diagnosis of active substance dependence or use of illicit substances within the past month
- History of type 2 diabetes mellitus prior to AAP use
- Past history of or currently has pernicious, aplastic, or normocytic anemia with a B12 deficiency
- Inability to give informed consent or unwillingness to participate
- Presence of any serious medical conditions that would significantly affect weight changes (i.e. neoplastic or uncontrolled thyroid disease)
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- Blood pressure lower than 90/60 mmHg
- History of Type 2 Diabetes Mellitus prior to AAP use
- History of hypersensitivity or allergic reaction to folic acid or any of the product ingredients
- Current pregnancy or nursing
- Current substance dependence diagnosis
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Folate Pharmacogenomics and Risk of Atypical Antipsychotic Metabolic Side Effects
This study will examine possible causes of metabolic side effects in people taking atypical antipsychotic (AAP) medications.
Read the detailed description
Antipsychotic medications are used to treat some of the most severe symptoms of mental illness, such as hallucinations and irrational outbursts. Atypical antipsychotics (AAPs) are a group of newer, second generation antipsychotic medications that effectively treat psychotic symptoms but that also have severe side effects. One side effect is an increased risk of metabolic syndrome, which is a cluster of conditions that together increase the risk of heart disease, stroke, type 2 diabetes, and endothelial dysfunction-dysfunction of the cells that line the inner surface of blood cells. Schizophrenic patients taking atypical antipsychotics are more than twice as likely as the general population to experience metabolic syndrome. Certain genetic variants associated with folate metabolism, as well as low dietary folate, may lead to the development of metabolic syndrome and its associated diseases. These factors have been studied in the general population, but not in a group of schizophrenic patients taking antipsychotics. This study will examine the relationship among folic acid, variants in the gene methylenetetrahydrofolate reductase, and metabolic syndrome and its associated diseases in people with schizophrenia who are taking atypical antipsychotics. The study will also evaluate the use of folic acid supplementation for treating metabolic syndrome in this population.
Participation in this study will involve two phases. The first phase will involve recruitment, screening, and testing of participants taking antipsychotics and will last 4 years. During this phase, participants will attend one study visit in which they will undergo a screening for metabolic syndrome and have the following measured: endothelial functioning, body size, diet, physical activity, medication history, and genetic makeup. Participants who have metabolic syndrome will be invited to participate in Phase 2.
Phase 2 will run concurrently with Phase 1, but will extend to 5 years, in order to give all participants an opportunity to continue from one phase to the next if they meet entry criteria. Participants in Phase 2 will attend four study visits over the course of 3 months: one at the beginning of the phase and one after each month of the study. After the first study visit, participants will be given folic acid to take daily for the 3 months. At each study visit, participants will be asked about thoughts, illness, functioning, diet, medication side effects, recent medication history, smoking history, alcohol intake, and exercise habits. On the first and last visits, participants will undergo additional tests of genetics, blood hormone levels, and blood vessel functioning, and additional measurements will be made of height, weight, vital signs, and body size. The Phase 2 study is now inactive.
Phase 2B is active and currently recruiting participants. This is a randomized, placebo controlled study of folate supplementation. Participants in phase 2B will attend 6 study visits over the course of 6 months. At the first study visit they will be randomized to either folic acid 5mg daily for 4 months or placebo. This 4 month period is followed by a 2 month follow up visit, when no supplementation is given. At each study visit, participants will be asked about thoughts, illness, functioning, diet, medication side effects, recent medication history, smoking history, alcohol intake, and exercise habits. On the first and last visits, participants will undergo additional tests of genetics, blood hormone levels, and blood vessel functioning, and additional measurements will be made of height, weight, vital signs, and body size.
- Conditions
- Schizophrenia
- Being tested
- Folic Acid, Placebo
- Keywords
- Antipsychotic, Metabolic Syndrome, Insulin Resistance, Endothelial Function
- Medical subject headings
- Schizophrenia, Metabolic Syndrome, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Folic AcidDietary supplement
Also called Folate
5 mg of folic acid taken daily for 3 months in an open label fashion
PlaceboOther
Subjects may receive placebo (a sugar pill) for 4 months
| Study group | Role | What they receive |
|---|---|---|
| Folate | Experimental | During Phase 1, participants will undergo screening for metabolic syndrome and have genetic makeup, body size, and endothelial functioning measured. During Phase 2, participants will receive daily folic acid as a treatment for metabolic syndrome.
Phase 2B participants will receive either daily folic acid or placebo as a treatment for metabolic syndrome. Receives: Dietary Supplement: Folic Acid |
| Placebo | Placebo comparator | During Phase 1, participants will undergo screening for metabolic syndrome and have genetic makeup, body size, and endothelial functioning measured. During Phase 2, participants will receive daily folic acid as a treatment for metabolic syndrome.
Phase 2B participants will receive either daily folic acid or placebo as a treatment for metabolic syndrome. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Endothelial functioning
Using the EndoPAT machine (Itamar) we will measure the Reactive hyperemia index (RHI)
Measured: Measured at baseline and after 3 months, and then at a two month follow up visit
Secondary outcomes (1)
metabolic syndrome
Metabolic Syndrome is defined as having any 3 of the following: 1) abdominal obesity characterized by waist circumference of >40 inches for men or >35 inches for women, 2) triglycerides ≥150 mg/dL, 3) HDL cholesterol <40 mg/dL for men and <50 mg/dL for women or receiving a lipid lowering agent), 4) blood pressure ≥130/≥85 mmHg or treatment for hypertension, or 5) fasting glucose ≥100 mg/dL or treatment of diabetes.
Measured: measured at baseline, endpoint, and follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Dec 2008 (estimated)
- Study startOct 2008
- Primary completionMay 2019
- Study completionMay 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by University of MichiganThe 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 N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 88 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Vicki Ellingrod, University of Michigan
- Investigators
- Vicki L. Ellingrod, PharmD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00815854
- Sponsor's protocol ID
- R01MH082784
- Other IDs
- R01MH082784, R01MH082784-01, DATR A5-ETSE
- Status last verified
- Jun 2019
- First submitted
- 29 Dec 2008
- Last updated
- 21 Jun 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Folate Pharmacogenomics and Risk of Atypical Antipsychotic Metabolic Side Effects
- ClinicalTrials.gov ID
- NCT00815854
- Acronym / sponsor ID
- R01MH082784
- Conditions
- Schizophrenia
- Keywords
- Antipsychotic, Metabolic Syndrome, Insulin Resistance, Endothelial Function
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 88 participants (actual)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Oct 2008
- Primary completion
- May 2019 (actual)
- Study completion
- May 2019 (actual)
- First posted
- 31 Dec 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 will examine possible causes of metabolic side effects in people taking atypical antipsychotic (AAP) medications.
Detailed description
Antipsychotic medications are used to treat some of the most severe symptoms of mental illness, such as hallucinations and irrational outbursts. Atypical antipsychotics (AAPs) are a group of newer, second generation antipsychotic medications that effectively treat psychotic symptoms but that also have severe side effects. One side effect is an increased risk of metabolic syndrome, which is a cluster of conditions that together increase the risk of heart disease, stroke, type 2 diabetes, and endothelial dysfunction-dysfunction of the cells that line the inner surface of blood cells. Schizophrenic patients taking atypical antipsychotics are more than twice as likely as the general population to experience metabolic syndrome. Certain genetic variants associated with folate metabolism, as well as low dietary folate, may lead to the development of metabolic syndrome and its associated diseases. These factors have been studied in the general population, but not in a group of schizophrenic patients taking antipsychotics. This study will examine the relationship among folic acid, variants in the gene methylenetetrahydrofolate reductase, and metabolic syndrome and its associated diseases in people with schizophrenia who are taking atypical antipsychotics. The study will also evaluate the use of folic acid supplementation for treating metabolic syndrome in this population.
Participation in this study will involve two phases. The first phase will involve recruitment, screening, and testing of participants taking antipsychotics and will last 4 years. During this phase, participants will attend one study visit in which they will undergo a screening for metabolic syndrome and have the following measured: endothelial functioning, body size, diet, physical activity, medication history, and genetic makeup. Participants who have metabolic syndrome will be invited to participate in Phase 2.
Phase 2 will run concurrently with Phase 1, but will extend to 5 years, in order to give all participants an opportunity to continue from one phase to the next if they meet entry criteria. Participants in Phase 2 will attend four study visits over the course of 3 months: one at the beginning of the phase and one after each month of the study. After the first study visit, participants will be given folic acid to take daily for the 3 months. At each study visit, participants will be asked about thoughts, illness, functioning, diet, medication side effects, recent medication history, smoking history, alcohol intake, and exercise habits. On the first and last visits, participants will undergo additional tests of genetics, blood hormone levels, and blood vessel functioning, and additional measurements will be made of height, weight, vital signs, and body size. The Phase 2 study is now inactive.
Phase 2B is active and currently recruiting participants. This is a randomized, placebo controlled study of folate supplementation. Participants in phase 2B will attend 6 study visits over the course of 6 months. At the first study visit they will be randomized to either folic acid 5mg daily for 4 months or placebo. This 4 month period is followed by a 2 month follow up visit, when no supplementation is given. At each study visit, participants will be asked about thoughts, illness, functioning, diet, medication side effects, recent medication history, smoking history, alcohol intake, and exercise habits. On the first and last visits, participants will undergo additional tests of genetics, blood hormone levels, and blood vessel functioning, and additional measurements will be made of height, weight, vital signs, and body size.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Folate | Experimental | Dietary Supplement: Folic AcidDuring Phase 1, participants will undergo screening for metabolic syndrome and have genetic makeup, body size, and endothelial functioning measured. During Phase 2, participants will receive daily folic acid as a treatment for metabolic syndrome. Phase 2B participants will receive either daily folic acid or placebo as a treatment for metabolic syndrome. |
| Placebo | Placebo comparator | Other: PlaceboDuring Phase 1, participants will undergo screening for metabolic syndrome and have genetic makeup, body size, and endothelial functioning measured. During Phase 2, participants will receive daily folic acid as a treatment for metabolic syndrome. Phase 2B participants will receive either daily folic acid or placebo as a treatment for metabolic syndrome. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- DSM-IV diagnosis of schizophrenia, schizophreniform disorder, schizoaffective disorder, or psychosis not otherwise specified
- Treatment with one of the following atypical antipsychotics (AAPs) for at least 6 months: clozapine, olanzapine, risperidone, quetiapine, aripiprazole, or ziprasidone
- Previous participation in Phase 1 pharmacogenomic study
- Meets metabolic syndrome criteria
- No medication changes for 6 months, including antipsychotic medication changes and changes in any other medications related to treating metabolic syndrome, diabetes, hypertension, or hyperlipidemia
Key exclusion criteria (11 listed)
- Presence of any serious medical condition that would significantly affect weight changes, such as neoplastic or thyroid disease
- Diagnosis of active substance dependence or use of illicit substances within the past month
- History of type 2 diabetes mellitus prior to AAP use
- Past history of or currently has pernicious, aplastic, or normocytic anemia with a B12 deficiency
- Inability to give informed consent or unwillingness to participate
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 |
|---|---|---|
| Folic AcidAlso: Folate5 mg of folic acid taken daily for 3 months in an open label fashion | Dietary supplement | Folate |
| PlaceboSubjects may receive placebo (a sugar pill) for 4 months | Other | Placebo |
Primary outcome
Endothelial functioning
Time frame: Measured at baseline and after 3 months, and then at a two month follow up visit
Using the EndoPAT machine (Itamar) we will measure the Reactive hyperemia index (RHI)
1 secondary outcome
metabolic syndrome
Time frame: measured at baseline, endpoint, and follow up
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 21 Jun 2019.
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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.
Vicki L. Ellingrod, PharmD principal investigator
University of Michigan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Folic Acid in people with Schizophrenia, run by University of Michigan 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 11 inclusion and 11 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 21 Jun 2019. 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?
Endothelial functioning (time frame: Measured at baseline and after 3 months, and then at a two month follow up visit). 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 21 Jun 2019.