Bipolar Depression, Insulin Resistance, Metabolic Syndrome
Conditions
Brief summary
The study is an open-label 8-week adjunctive trial of pioglitazone for the acute relief of bipolar depression comorbid with metabolic syndrome/insulin resistance. Subjects who experience a partial or full response will have the option of continuing in an acute continuation phase lasting up to 12 weeks. The extension phase will allow assessment of the safety and tolerability of pioglitazone during the acute continuation period.
Interventions
DRUGPioglitazone
An open-label 12-week trial of pioglitazone monotherapy. The investigators will titrate pioglitazone to the maximum tolerable dose up to 45mg per day.
Sponsors
National Alliance for Research on Schizophrenia and Depression
Takeda Pharmaceuticals North America, Inc.
University Hospitals Cleveland Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Be male or female between the ages of 18 and 70 * Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV diagnosis of bipolar disorder (type I, II, or NOS) * Currently depressed as confirmed by the MINI-Plus at the screening visit * Currently receiving treatment with an anti-manic drug * Meets criteria for metabolic syndrome or insulin resistance
Exclusion criteria
* Pregnancy or breast feeding * Unstable or inadequately treated medical illness as judged by the investigator * Severe personality disorder * Serious suicidal risk * Known history of intolerance or hypersensitivity to pioglitazone * Treatment with pioglitazone in the 3 months prior to randomization * Dependence on alcohol or drugs (other than nicotine) in the 3 months prior to study entry * Currently taking an antidiabetic/glucose-lowering agent. * Diagnosed with dementia * Acute Mania as defined by a Young Mania Rating Scale (YMRS) score \> 15 * Diagnosed with heart failure * Transaminase elevation \>2.5 times the upper limit of normal * Presence of renal impairment (eg. creatinine \> 1.5) * Fasting blood glucose \>150 mg/dL * Hb A1c \> 7.5%
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Inventory of Depressive Symptomatology-Clinician Rated (IDS-CR) Score | Week 0 - Week 8 | Inventory of Depressive Symptoms-Clinician rated, 30 item (IDS-C30) score change from baseline to study endpoint. IDS-C30 total scores can range from 0 to 84, with higher scores indicating a worse outcome |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Quick Inventory of Depressive Symptoms-Self Report (QIDS-SR16) Total Score | Week 0 - Week 8 | The QIDS-SR16 is a 16-item, self report assessment. Total scores can range from 0 to 27, with higher scores indicating a worse outcome |
| Response Rates on the IDS-CR, Montgomery Asberg Depression Rating Scale (MADRS) and Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) | Week 0 - Week 8 | A participant is considered to have responded if their total score on either the MADRS or QIDS-SR16 decreases by at least 50% between their Week 0 visit and Week 8 visit. |
| Remission Rates Based on IDS-CR, QIDS-SR, and MADRS Scores | Week 0 - Week 8 | A participant is considered in remission if their total score on the MADRS is \> 7, their total score on the QIDS-SR16 \> 6 and/or their total score on the IDS-CR is \> 12 at Week 8. |
| Change in Clinical Global Impressions-Bipolar Version (CGI-BP) | Week 0 - Week 8 | The CGI-BP asks the clinician one question: Considering your total clinical experience with this particular population, how mentally ill is the patient at this time? which is rated on the following seven-point scale: 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pioglitazone Pioglitazone has been approved by the U.S. Food and Drug Administration (FDA) to help people who are diagnosed with diabetes
Pioglitazone: An open-label 12-week trial of pioglitazone monotherapy. The investigators will titrate pioglitazone to the maximum tolerable dose up to 45mg per day. | 34 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Lack of Efficacy | 1 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Pioglitazone |
|---|---|
| Age, Continuous | 47.8 years STANDARD_DEVIATION 10.9 |
| Age first treated for depression | 34.7 years STANDARD_DEVIATION 11.3 |
| Age first treated for mania/hypomania | 40.8 years STANDARD_DEVIATION 12 |
| Age of depression onset | 17.8 years STANDARD_DEVIATION 10.9 |
| Age of mania/hypomania onset | 23.5 years STANDARD_DEVIATION 19.2 |
| Bipolar Subtype Bipolar 1 | 27 participants |
| Bipolar Subtype Bipolar 2 | 5 participants |
| Bipolar Subtype Bipolar not otherwise specified | 2 participants |
| Comorbid diagnoses Alcohol use disorder, lifetime | 19 participants |
| Comorbid diagnoses Generalized anxiety disorder | 25 participants |
| Comorbid diagnoses Obsessive-compulsive disorder | 5 participants |
| Comorbid diagnoses Panic disorder | 11 participants |
| Comorbid diagnoses Post-traumatic stress disorder | 12 participants |
| Duration of mood state | 315.5 days STANDARD_DEVIATION 331.6 |
| Employed No | 22 participants |
| Employed Yes | 12 participants |
| Gender Female | 19 Participants |
| Gender Male | 15 Participants |
| History of physical abuse No | 24 participants |
| History of physical abuse Yes | 10 participants |
| History of sexual abuse No | 25 participants |
| History of sexual abuse Yes | 9 participants |
| History of verbal abuse No | 20 participants |
| History of verbal abuse Yes | 14 participants |
| Insulin resistance No | 4 participants |
| Insulin resistance Yes | 30 participants |
| Medication treatment failures during current episode >=2 mood stabilizers (MS) or a MS + antidepressant | 26 participants |
| Medication treatment failures during current episode >=4 mood stabilizers or antidepressant | 15 participants |
| Metabolic syndrome No | 2 participants |
| Metabolic syndrome Yes | 32 participants |
| Number of prior hospitalizations | 2 hospitalizations STANDARD_DEVIATION 4 |
| Number of prior suicide attempts | 1.2 suicide attempts STANDARD_DEVIATION 2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 16 / 34 |
| serious Total, serious adverse events | 0 / 34 |
Outcome results
Primary
Change in the Inventory of Depressive Symptomatology-Clinician Rated (IDS-CR) Score
Inventory of Depressive Symptoms-Clinician rated, 30 item (IDS-C30) score change from baseline to study endpoint. IDS-C30 total scores can range from 0 to 84, with higher scores indicating a worse outcome
Time frame: Week 0 - Week 8
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone | Change in the Inventory of Depressive Symptomatology-Clinician Rated (IDS-CR) Score | -16.5 units on a scale | Standard Error 2.6 |
Secondary
Change in Clinical Global Impressions-Bipolar Version (CGI-BP)
The CGI-BP asks the clinician one question: Considering your total clinical experience with this particular population, how mentally ill is the patient at this time? which is rated on the following seven-point scale: 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients.
Time frame: Week 0 - Week 8
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone | Change in Clinical Global Impressions-Bipolar Version (CGI-BP) | -1.9 units on a scale | Standard Error 0.3 |
Secondary
Change in Quick Inventory of Depressive Symptoms-Self Report (QIDS-SR16) Total Score
The QIDS-SR16 is a 16-item, self report assessment. Total scores can range from 0 to 27, with higher scores indicating a worse outcome
Time frame: Week 0 - Week 8
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone | Change in Quick Inventory of Depressive Symptoms-Self Report (QIDS-SR16) Total Score | -7.1 units on a scale | Standard Error 1.2 |
Secondary
Remission Rates Based on IDS-CR, QIDS-SR, and MADRS Scores
A participant is considered in remission if their total score on the MADRS is \> 7, their total score on the QIDS-SR16 \> 6 and/or their total score on the IDS-CR is \> 12 at Week 8.
Time frame: Week 0 - Week 8
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pioglitazone | Remission Rates Based on IDS-CR, QIDS-SR, and MADRS Scores | 8 participants |
Secondary
Response Rates on the IDS-CR, Montgomery Asberg Depression Rating Scale (MADRS) and Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR)
A participant is considered to have responded if their total score on either the MADRS or QIDS-SR16 decreases by at least 50% between their Week 0 visit and Week 8 visit.
Time frame: Week 0 - Week 8
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pioglitazone | Response Rates on the IDS-CR, Montgomery Asberg Depression Rating Scale (MADRS) and Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) | 13 participants |