Major Depressive DisorderPhase 4NCT01559857
Pioglitazone in Patients With Mood Disorders
A Phase 4 study testing Pioglitazone and Sugar Pill in people with Major Depressive Disorder and Insulin Resistance, run by Stanford University at 1 site in United States.
Trial summary
The purpose of this study is to see how an insulin sensitizing medication, Pioglitazone, can cause changes in mood in some depressed patients. Study participants receive assessment of their cognitive and metabolic functioning. Read more about this study
- Who is it for?
- Ages 20 to 65 years
- Conditions the study is for
- Major Depressive Disorder, Insulin Resistance
- What is being tested?
- Pioglitazone and Sugar Pill
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 37 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2011to Jun 2014
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 20 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age between 20 and 65 years
- BMI between 25 and 35
- Diagnosis of unipolar, non-psychotic, non-melancholic major depressive disorder (MDD) or depressive episode of bipolar disorder (Bipolar I, II or NOS)
- Depression severity as defined by score of < 12 on the 21-item Hamilton Rating Scale for Depression and no psychiatric admission within 6 months from study entry and no suicide attempt within the last 12 months
- Willingness to sign human subjects consent form
Who cannot join
- Diagnosis of possible or probable cognitive impairment
- For women only: pregnancy, breastfeeding
- Personal history of Type I or Type II diabetes
- Unstable cardiovascular disease or other major medical condition, or history of myocardial infarction within the previous year
- Significant cerebrovascular disease, as evidenced by neurological examination, uncontrolled hypertension (systolic blood pressure > 170 or diastolic blood pressures > 100)
- Current drug or alcohol abuse
- History of neurological disorder, e.g. multiple sclerosis, stroke etc
- Use of any drug that may significantly affect psychometric testing or the insulin testing
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford University Department of Psychiatry & Behavioral Sciences
Palo Alto, California, 94305
About this study
Official title: Pioglitazone Treatment for Insulin Resistant Patients With Mood Disorders
The purpose of this study is to see how an insulin sensitizing medication, Pioglitazone, can cause changes in mood in some depressed patients. Study participants receive assessment of their cognitive and metabolic functioning.
If they meet criteria, they will be asked to take either Pioglitazone or a placebo for a 90-day trial. Participants will undergo an Oral Glucose Tolerance Test to measure fasting insulin and glucose levels, as well as routine blood testing.
The investigators hope to quantify the role of Pioglitazone in patients with mood disorders and compare the values to those previously obtained in a healthy age-matched control population. The investigators also hope to examine the association between IR and cognitive performance and clinical course of depression in patients with mood disorders.
Read the detailed description
While the association between insulin resistance (IR) and depressive symptoms is well documented (Gold et al., 2005), causal aspects of the relationship are incompletely documented and likely bidirectional. As the current prevalence rates of DM2 and related diseases grow worldwide and its associated metabolic consequences become more salient, it is increasingly critical to understand the role of IR in depressive disorders.
Insulin has been shown to alter central nervous system (CNS) concentrations of neurotransmitters such as dopamine (Lozovsky et al., 1981) and norepinephrine (Boyd et al., 1985), by a variety of mechanisms, as well as to have direct electrophysiological effects on neuronal activity (Boyd et al., 1985). Additionally, induced IR in the CNS has been shown to result in cognitive and behavioral alterations in animal models (Kovacs and Hajnal, 2009).
Accordingly, when depression manifests as a sequela of metabolic disorders such as obesity and DM2, it is hypothesized to be associated with resistance of CNS structures to the effects of insulin, which may derive from genetic polymorphisms, as well as from long-term exposure to excess amounts of circulating insulin due to peripheral IR (Okamura et al., 2000b). Thus, "overcoming" central IR," for example by pharmacological interventions, could be an attractive strategy in the treatment and prevention of these disorders.
This study aimed to assess mood effects in a 12-week double-blind, randomized-controlled trial of adjuvant treatment with the PPARγ-agonist pioglitazone, an insulin-sensitizing agent, compared with treatment with placebo, in participants with non-psychotic, non-remitting depression receiving standard psychiatric regimens for unipolar or bipolar depression. Pioglitazone is an FDA-approved, insulin-sensitizing treatment for DM2 and has particularly beneficial effects on lipid profile (Goldberg et al., 2005) and rate of cardiovascular events (Lincoff et al., 2007) in this population. Furthermore, in assessing the utility of an additive insulin-sensitizing agent on mood outcomes in both insulin sensitive and insulin resistant patients, this study attempted to disentangle the role of insulin-sensitizing and anti-inflammatory mechanisms.
In an a prior manner, this study's aims were twofold: (1) to assess whether treatment with pioglitazone would result in significantly greater mood improvement compared to treatment with placebo among patients with unremitted depression despite treatment as usual (TAU) and (2) to examine mechanisms of proposed effects of a PPARγ-agonist on mood outcomes by comparing treatment outcomes based on surrogate markers of glucose metabolic status (hereafter referred to IR and IS) between IR and insulin sensitive (IS) participants.
- Conditions
- Major Depressive Disorder, Insulin Resistance
- Being tested
- Pioglitazone, Sugar Pill
- Keywords
- Depression, Insulin resistance, Mood disorder
- Medical subject headings
- Depressive Disorder, Major, Insulin Resistance, Depression, Mood Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PioglitazoneDrug
Also called Actos
30mg once daily for 12 weeks
Sugar PillDrug
Also called Placebo
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Pioglitazone | Active comparator | 50% of participants will be allocated to 12 weeks of treatment with 30 mg/day of Pioglitazone. Receives: Drug: Pioglitazone |
| Sugar pill | Placebo comparator | 50% of participants will be randomized to 12 weeks of treatment with placebo pill. Receives: Drug: Sugar Pill |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hamilton Depression Rating Scale at Baseline
The HDRS-21 was used to screen for unremitted depression. The HDRS-21 is scored on a scale from 0 to 21, where 0 is the lowest level of depression severity and 21 is the highest level of depression severity. Unremitted depression is characterized by a score of ≥7. The HDRS-21 scores at baseline are shown in the data table below.
Measured: Baseline
Secondary outcomes (2)
Fasting Insulin Measurements at Baseline
The fasting plasma insulin measurements taken at baseline are shown in the data table below.
Measured: Baseline
Change in HDRS-21: From Baseline to 12 Weeks
The HDRS-21 was administered at baseline and at the end of 12 weeks, and the mean difference between the two time points was calculated. The HDRS-21 is scored on a scale from 0 to 21, where 0 is the lowest level of depression severity and 21 is the highest level of depression severity.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2012 (estimated)
- Study startNov 2011
- Primary completionJan 2014
- Study completionJun 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Natalie Rasgon, Stanford University
- Investigators
- Natalie Rasgon, MD, PhD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01559857
- Sponsor's protocol ID
- R21MH093948-01A1
- Other IDs
- R21MH093948-01A1
- Status last verified
- Mar 2017
- First submitted
- 16 Mar 2012
- Last updated
- 10 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Rasgon N, Lin KW, Lin J, Epel E, Blackburn E. Telomere length as a predictor of response to Pioglitazone in patients with unremitted depression: a preliminary study. Transl Psychiatry. 2016 Jan 5;6(1):e709. doi: 10.1038/tp.2015.187.
PubMed 26731446
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pioglitazone Treatment for Insulin Resistant Patients With Mood Disorders
- ClinicalTrials.gov ID
- NCT01559857
- Acronym / sponsor ID
- R21MH093948-01A1
- Conditions
- Major Depressive Disorder, Insulin Resistance
- Keywords
- Depression, Insulin resistance, Mood disorder
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Mental Health (NIMH)
- Study start
- Nov 2011
- Primary completion
- Jan 2014 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 21 Mar 2012 (estimated)
- Results
- Posted 10 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to see how an insulin sensitizing medication, Pioglitazone, can cause changes in mood in some depressed patients. Study participants receive assessment of their cognitive and metabolic functioning.
If they meet criteria, they will be asked to take either Pioglitazone or a placebo for a 90-day trial. Participants will undergo an Oral Glucose Tolerance Test to measure fasting insulin and glucose levels, as well as routine blood testing.
The investigators hope to quantify the role of Pioglitazone in patients with mood disorders and compare the values to those previously obtained in a healthy age-matched control population. The investigators also hope to examine the association between IR and cognitive performance and clinical course of depression in patients with mood disorders.
Detailed description
While the association between insulin resistance (IR) and depressive symptoms is well documented (Gold et al., 2005), causal aspects of the relationship are incompletely documented and likely bidirectional. As the current prevalence rates of DM2 and related diseases grow worldwide and its associated metabolic consequences become more salient, it is increasingly critical to understand the role of IR in depressive disorders.
Insulin has been shown to alter central nervous system (CNS) concentrations of neurotransmitters such as dopamine (Lozovsky et al., 1981) and norepinephrine (Boyd et al., 1985), by a variety of mechanisms, as well as to have direct electrophysiological effects on neuronal activity (Boyd et al., 1985). Additionally, induced IR in the CNS has been shown to result in cognitive and behavioral alterations in animal models (Kovacs and Hajnal, 2009).
Accordingly, when depression manifests as a sequela of metabolic disorders such as obesity and DM2, it is hypothesized to be associated with resistance of CNS structures to the effects of insulin, which may derive from genetic polymorphisms, as well as from long-term exposure to excess amounts of circulating insulin due to peripheral IR (Okamura et al., 2000b). Thus, "overcoming" central IR," for example by pharmacological interventions, could be an attractive strategy in the treatment and prevention of these disorders.
This study aimed to assess mood effects in a 12-week double-blind, randomized-controlled trial of adjuvant treatment with the PPARγ-agonist pioglitazone, an insulin-sensitizing agent, compared with treatment with placebo, in participants with non-psychotic, non-remitting depression receiving standard psychiatric regimens for unipolar or bipolar depression. Pioglitazone is an FDA-approved, insulin-sensitizing treatment for DM2 and has particularly beneficial effects on lipid profile (Goldberg et al., 2005) and rate of cardiovascular events (Lincoff et al., 2007) in this population. Furthermore, in assessing the utility of an additive insulin-sensitizing agent on mood outcomes in both insulin sensitive and insulin resistant patients, this study attempted to disentangle the role of insulin-sensitizing and anti-inflammatory mechanisms.
In an a prior manner, this study's aims were twofold: (1) to assess whether treatment with pioglitazone would result in significantly greater mood improvement compared to treatment with placebo among patients with unremitted depression despite treatment as usual (TAU) and (2) to examine mechanisms of proposed effects of a PPARγ-agonist on mood outcomes by comparing treatment outcomes based on surrogate markers of glucose metabolic status (hereafter referred to IR and IS) between IR and insulin sensitive (IS) participants.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pioglitazone | Active comparator | Drug: Pioglitazone50% of participants will be allocated to 12 weeks of treatment with 30 mg/day of Pioglitazone. |
| Sugar pill | Placebo comparator | Drug: Sugar Pill50% of participants will be randomized to 12 weeks of treatment with placebo pill. |
Who may qualify
- Ages
- 20 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age between 20 and 65 years
- BMI between 25 and 35
- Diagnosis of unipolar, non-psychotic, non-melancholic major depressive disorder (MDD) or depressive episode of bipolar disorder (Bipolar I, II or NOS)
- Depression severity as defined by score of < 12 on the 21-item Hamilton Rating Scale for Depression and no psychiatric admission within 6 months from study entry and no suicide attempt within the last 12 months
- Willingness to sign human subjects consent form
Key exclusion criteria (8 listed)
- Diagnosis of possible or probable cognitive impairment
- For women only: pregnancy, breastfeeding
- Personal history of Type I or Type II diabetes
- Unstable cardiovascular disease or other major medical condition, or history of myocardial infarction within the previous year
- Significant cerebrovascular disease, as evidenced by neurological examination, uncontrolled hypertension (systolic blood pressure > 170 or diastolic blood pressures > 100)
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 |
|---|---|---|
| PioglitazoneAlso: Actos30mg once daily for 12 weeks | Drug | Pioglitazone |
| Sugar PillAlso: PlaceboPlacebo | Drug | Sugar pill |
Primary outcome
Hamilton Depression Rating Scale at Baseline
Time frame: Baseline
The HDRS-21 was used to screen for unremitted depression. The HDRS-21 is scored on a scale from 0 to 21, where 0 is the lowest level of depression severity and 21 is the highest level of depression severity. Unremitted depression is characterized by a score of ≥7. The HDRS-21 scores at baseline are shown in the data table below.
2 secondary outcomes
Fasting Insulin Measurements at Baseline
Time frame: Baseline
Change in HDRS-21: From Baseline to 12 Weeks
Time frame: 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26731446Rasgon N, Lin KW, Lin J, Epel E, Blackburn E. Telomere length as a predictor of response to Pioglitazone in patients with unremitted depression: a preliminary study. Transl Psychiatry. 2016 Jan 5;6(1):e709. doi: 10.1038/tp.2015.187.
- Individual participant dataSharing planned: No
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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.
Natalie Rasgon, MD, PhD principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Pioglitazone and Sugar Pill in people with Major Depressive Disorder and Insulin Resistance, run by Stanford 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 5 inclusion and 8 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 10 May 2017. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Hamilton Depression Rating Scale at Baseline (time frame: Baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01559857, which also lists 1 linked publication.
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 10 May 2017.