Examining Risk Factors for Atypical Antipsychotic Metabolic Side Effects

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 by University of Michigan
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Vicki Ellingrod, University of Michigan
ClinicalTrials.gov Identifier:
NCT00815854
First received: December 29, 2008
Last updated: August 23, 2013
Last verified: August 2013
  Purpose

This study will examine possible causes of metabolic side effects in people taking atypical antipsychotic (AAP) medications.


Condition Intervention
Schizophrenia
Dietary Supplement: Folic Acid
Dietary Supplement: folic acid
Other: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Official Title: Folate Pharmacogenomics and Risk of Atypical Antipsychotic Metabolic Side Effects

Resource links provided by NLM:


Further study details as provided by University of Michigan:

Primary Outcome Measures:
  • Endothelial functioning [ Time Frame: Measured at baseline and after 3 months, and then at a two month follow up visit ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • metabolic syndrome [ Time Frame: measured at baseline, endpoint, and follow up ] [ Designated as safety issue: No ]

Estimated Enrollment: 150
Study Start Date: October 2008
Estimated Study Completion Date: September 2018
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1

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.

Dietary Supplement: Folic Acid
5 mg of folic acid taken daily for 3 months in an open label fashion
Other Name: Folate
Dietary Supplement: folic acid
subjects may receive folic acid 5mg daily for 4 months
Other: Placebo
Subjects may receive placebo (a sugar pill) for 4 months

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.

Phase2B is now currently starting. 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.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria for Phase 1:

  • 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

Inclusion Criteria for Phase 2:

  • 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

Exclusion Criteria for Phases 1 and 2:

  • 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

Inclusion criteria for Phase 2B:

  • At least 18 years old and presence of a DSM-IV diagnosis of schizophrenia, schizophreniform disorder, schizoaffective disorder, or psychosis NOS
  • 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

Exclusion Criteria for Phase 2B

  • 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)
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00815854

Contacts
Contact: Vicki L. Ellingrod, PharmD 734-615-4728 vellingr@med.umich.edu
Contact: Zarina Kraal, BS, MA 734-358-2136 azkraal@med.umich.edu

Locations
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Principal Investigator: Vicki L. Ellingrod, PharmD         
Sponsors and Collaborators
University of Michigan
Investigators
Principal Investigator: Vicki L. Ellingrod, PharmD University of Michigan
  More Information

No publications provided

Responsible Party: Vicki Ellingrod, Associate Professor, University of Michigan
ClinicalTrials.gov Identifier: NCT00815854     History of Changes
Other Study ID Numbers: R01 MH082784, R01MH082784, R01 MH082784-01, DATR A5-ETSE
Study First Received: December 29, 2008
Last Updated: August 23, 2013
Health Authority: United States: Federal Government

Keywords provided by University of Michigan:
Antipsychotic
Metabolic Syndrome
Insulin Resistance
Endothelial Function

Additional relevant MeSH terms:
Folic Acid
Vitamin B Complex
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Hematinics
Hematologic Agents
Vitamins
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on September 18, 2014