Antipsychotic AgentsNCT02374996
Pharmacoepigenetics of Bipolar Disorder Treatment
An observational study of Antipsychotic Agents and Bipolar Disorder, run by Wayne State University at 1 site in United States.
Trial summary
Insulin is a hormone produced by the body to regulate blood sugar. Insulin resistance is a state when the body is not using insulin correctly, and more insulin is needed to maintain normal blood sugar. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Antipsychotic Agents, Bipolar Disorder
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2015to Sep 2017
- Phase
- Observational
- 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
Study population: Bipolar patients treated with Lithium or an antipsychotic
Who may be able to join
- Aged 18-65 with a Bipolar Spectrum Diagnosis (Bipolar I, II or NOS)
- Currently treated with lithium or an antipsychotic as determined by a physician for at least 3 months at a stable dosage.
- Non- obese with BMI < 30
- Able to communicate meaningfully with the investigator and legally competent to provide informed written consent.
- Females must be non-lactating, have a pregnancy test and be on acceptable birth control
- 105 subjects will be studied in total from three groups:
Show all 9Show fewer
- One group will consist of 35 bipolar patients currently stable on an antipsychotics with impaired glucose tolerance (2-hour postprandial plasma glucose of 140-199mg/dL).
- The second group will consist of 35 age, gender, and body composition matched bipolar patients currently stable on an antipsychotic with normal glucose tolerance (2-hour postprandial plasma glucose <140mg/dL.
- The third group will consist of 35 age, gender and body composition matched bipolar subjects stable on lithium with normal glucose tolerance.
Who cannot join
- Currently diagnosed with diabetes (type I or II) or receiving treatment for diabetes. Any history of metabolic complications (weight gain, high cholesterol, high blood pressure) before taking an antipsychotic.
- Active diagnosis of alcohol or substance abuse.
- Primary relative diagnosed with type II diabetes.
- Treated with any of the following medications: a) Systemic glucocorticoids (more than 2 weeks), antineoplastic agents, transplant medications, anti-retroviral medications within 6 months prior to screening.
- Start or change of hormonal replacement therapy within 3 months prior to screening.
- History or presence of any of the following conditions
Show all 22Show fewer
- Clinically significant heart disease (New York Heart Classification greater than grade II; more than non-specific ST-T wave changes on the EKG)
- Peripheral vascular disease (history of claudication)
- Clinically significant pulmonary disease.
- Current uncontrolled hypertension (systolic BP>160 mmHg, diastolic BP>100 mmHg)
- History or presence of malignancy other than basal cell or squamous cell skin cancer
- Clinically significant hematologic disease
- Any of the following abnormal laboratory values:
- Hematocrit < 35 vol%
- Serum creatinine > 1.6 mg/dl
- aspartate aminotransferase (AST), alanine aminotransferase (ALT) or Alkaline phosphatase > 2.5 times the upper limit of normal
- Prothrombin time (PT), Partial thromboplastin time (PTT) outside the normal reference range
- thyroid-stimulating hormone (TSH) outside the normal reference range
- Triglycerides > 400 mg/dl
- Platelet count < 50,000
- Blood donation within 2 months prior to screening
- Engage in exercise with moderate to hard intensity for greater than 1 hour per day for 5 or more days per week.
Trial locations and contacts
1 site in 1 country.
United States1 site
Wayne State University Clinical Research Center
Detroit, Michigan, 48202
About this study
Official title: Pharmacoepigenetics of Second Generation Antipsychotic-Induced Insulin Resistance in Bipolar Disorder
Insulin is a hormone produced by the body to regulate blood sugar. Insulin resistance is a state when the body is not using insulin correctly, and more insulin is needed to maintain normal blood sugar. Insulin resistance is common in bipolar patients and even more common in bipolar patients treated with antipsychotics. Insulin resistance from antipsychotics can lead to type 2 diabetes, metabolic syndrome and cardiovascular disease and is known to lead to worse psychiatric outcomes (less mood stability) and lower life expectancies in bipolar disorder. Abnormal regulation of the folate cycle is known to play a role in antipsychotic-induced insulin resistance and the main endpoint to the folate cycle is the production of methyl donors for DNA methylation. DNA methylation is critical as it regulates how genes are expressed. Thus, changes in DNA methylation may play a role in the disease process of antipsychotic-induced insulin resistance. The purpose of this study is to examine the differences in the DNA methylation of candidate tissues known to have a role in the development of insulin resistance. The three groups of bipolar patients to be studied are 1) antipsychotic treated patients with impaired glucose tolerance, 2) antipsychotic treated patients with normal glucose tolerance and 3) lithium treated patients with normal glucose tolerance. Group 1 will be compared to groups 2 and 3 in order to assess how DNA methylation in the skeletal muscle and fat tissue changes due to medication effects (group 2 vs. 3) and medication side effects (group 1 vs. 2). Secondary analyses include the analysis of how fats are processed in skeletal muscle and fat tissue in relation to antipsychotic-induced insulin resistance and the correlation of DNA methylation across different tissues. The investigators hypothesize that antipsychotic-induced insulin resistance is to due changes in the way DNA is expressed (through epigenetic changes) which causes further changes in the way fats are processed in the body eventually leading to insulin resistance. This work is based on preliminary findings however further work is needed to identify the true mechanisms behind antipsychotic-induced insulin resistance and in particular, the main tissue in which this mechanism occurs.
Read the detailed description
This study will be composed of 2 visits. The first visit will be used as a screening visit for inclusion of the three groups of patients for the second visit where the outcomes will be collected (e.g., tissue samples for DNA methylation and lipidomic analysis).
- Conditions
- Antipsychotic Agents, Bipolar Disorder
- Medical subject headings
- Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| APIGT | Bipolar subjects treated with antipsychotics and having impaired glucose tolerance | |
| APNGT | Bipolar subjects treated with antipsychotics and having normal glucose tolerance | |
| LINGT | Bipolar subjects treated with lithium and having normal glucose tolerance |
What is being measured
The primary outcome is the main question the study is designed to answer.
DNA methylation in skeletal muscle and adipose tissue
The prevalence of DNA methylation of cytosine-phosphate-guanosine (CpG) Island 81 of the Fatty Acyl Coenzyme A Reductase gene will be compared amongst the groups. The is reported as % methylation
Measured: Baseline
Secondary outcomes (1)
shotgun Lipidomics in skeletal muscle and adipose tissue
shotgun lipidomics will be ran via the a lipidomics core in both muscle and adipose tissue. The quantified lipid metabolites (over 1000 will be quantified) will compared amongst groups using multivariate analyses
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2015 (estimated)
- Study startNov 2015
- Primary completionSep 2017
- Study completionSep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Antipsychotic AgentsStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wayne State University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kyle Burghardt, Wayne State University
- Investigators
- Kyle J Burghardt, PharmD, Principal investigator, Wayne State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02374996
- Sponsor's protocol ID
- BPBIOPWSU
- Status last verified
- Feb 2018
- First submitted
- 9 Feb 2015
- Last updated
- 14 Feb 2018
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacoepigenetics of Second Generation Antipsychotic-Induced Insulin Resistance in Bipolar Disorder
- ClinicalTrials.gov ID
- NCT02374996
- Acronym / sponsor ID
- BPBIOPWSU
- Conditions
- Antipsychotic Agents, Bipolar Disorder
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Wayne State UniversityUniversity, hospital or other
- Study start
- Nov 2015
- Primary completion
- Sep 2017 (actual)
- Study completion
- Sep 2017 (actual)
- First posted
- 2 Mar 2015 (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.
Insulin is a hormone produced by the body to regulate blood sugar. Insulin resistance is a state when the body is not using insulin correctly, and more insulin is needed to maintain normal blood sugar. Insulin resistance is common in bipolar patients and even more common in bipolar patients treated with antipsychotics. Insulin resistance from antipsychotics can lead to type 2 diabetes, metabolic syndrome and cardiovascular disease and is known to lead to worse psychiatric outcomes (less mood stability) and lower life expectancies in bipolar disorder. Abnormal regulation of the folate cycle is known to play a role in antipsychotic-induced insulin resistance and the main endpoint to the folate cycle is the production of methyl donors for DNA methylation. DNA methylation is critical as it regulates how genes are expressed. Thus, changes in DNA methylation may play a role in the disease process of antipsychotic-induced insulin resistance. The purpose of this study is to examine the differences in the DNA methylation of candidate tissues known to have a role in the development of insulin resistance. The three groups of bipolar patients to be studied are 1) antipsychotic treated patients with impaired glucose tolerance, 2) antipsychotic treated patients with normal glucose tolerance and 3) lithium treated patients with normal glucose tolerance. Group 1 will be compared to groups 2 and 3 in order to assess how DNA methylation in the skeletal muscle and fat tissue changes due to medication effects (group 2 vs. 3) and medication side effects (group 1 vs. 2). Secondary analyses include the analysis of how fats are processed in skeletal muscle and fat tissue in relation to antipsychotic-induced insulin resistance and the correlation of DNA methylation across different tissues. The investigators hypothesize that antipsychotic-induced insulin resistance is to due changes in the way DNA is expressed (through epigenetic changes) which causes further changes in the way fats are processed in the body eventually leading to insulin resistance. This work is based on preliminary findings however further work is needed to identify the true mechanisms behind antipsychotic-induced insulin resistance and in particular, the main tissue in which this mechanism occurs.
Detailed description
This study will be composed of 2 visits. The first visit will be used as a screening visit for inclusion of the three groups of patients for the second visit where the outcomes will be collected (e.g., tissue samples for DNA methylation and lipidomic analysis).
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| APIGT | – | –Bipolar subjects treated with antipsychotics and having impaired glucose tolerance |
| APNGT | – | –Bipolar subjects treated with antipsychotics and having normal glucose tolerance |
| LINGT | – | –Bipolar subjects treated with lithium and having normal glucose tolerance |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Bipolar patients treated with Lithium or an antipsychotic
Key inclusion criteria (9 listed)
- Aged 18-65 with a Bipolar Spectrum Diagnosis (Bipolar I, II or NOS)
- Currently treated with lithium or an antipsychotic as determined by a physician for at least 3 months at a stable dosage.
- Non- obese with BMI < 30
- Able to communicate meaningfully with the investigator and legally competent to provide informed written consent.
- Females must be non-lactating, have a pregnancy test and be on acceptable birth control
Key exclusion criteria (22 listed)
- Currently diagnosed with diabetes (type I or II) or receiving treatment for diabetes. Any history of metabolic complications (weight gain, high cholesterol, high blood pressure) before taking an antipsychotic.
- Active diagnosis of alcohol or substance abuse.
- Primary relative diagnosed with type II diabetes.
- Treated with any of the following medications: a) Systemic glucocorticoids (more than 2 weeks), antineoplastic agents, transplant medications, anti-retroviral medications within 6 months prior to screening.
- History or presence of any of the following conditions
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
DNA methylation in skeletal muscle and adipose tissue
Time frame: Baseline
The prevalence of DNA methylation of cytosine-phosphate-guanosine (CpG) Island 81 of the Fatty Acyl Coenzyme A Reductase gene will be compared amongst the groups. The is reported as % methylation
1 secondary outcome
shotgun Lipidomics in skeletal muscle and adipose tissue
Time frame: Baseline
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 14 Feb 2018.
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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.
Kyle J Burghardt, PharmD principal investigator
Wayne State University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Antipsychotic Agents and Bipolar Disorder, run by Wayne State University 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 9 inclusion and 22 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 14 Feb 2018. 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. 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?
DNA methylation in skeletal muscle and adipose tissue (time frame: Baseline). 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 14 Feb 2018.