DepressionPhase 2IRLGREY-BNCT02176291
Incomplete Response in Late-Life Depression: Getting to Remission With Buprenorphine
A Phase 2 study testing Buprenorphine in people with Depression and Major Depressive Disorder, run by Jordan F. Karp at 1 site in United States.
Trial summary
The purposes of this project are to examine the feasibility, safety, tolerability and clinical effect of low-dose buprenorphine as a novel treatment for late-life treatment-resistant depression and to develop preliminary data about mechanism of action. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Depression, Major Depressive Disorder
- What is being tested?
- Buprenorphine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2014to Feb 2018
- Phase
- Phase 2
- 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 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age >/= to 50 years.
- Major depressive disorder (MDD), single or recurrent, as diagnosed by the Structured Clinical Interview for the DSM IV (SCID-IV).
- Montgomery-Åsberg Depression Rating Scale (MADRS) >/= to 15.
- Has or agrees to establish a clinical relationship with primary care physician (PCP).
- Availability of an informant (e.g., emergency contact).
Who cannot join
- Inability to provide informed consent.
- Depressive symptoms not severe enough i.e.,Montgomery-Åsberg Depression Rating Scale ( MADRS) < 15 at the baseline assessments.
- Dementia, as defined by The Modified Mini-Mental State (3MS) examination < 84 and clinical evidence of dementia (e.g., memory impairment, executive dysfunction, agnosia, apraxia, aphasia, with functional impairment).
- Lifetime diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms, as diagnosed by the Structured Clinical Interview for DSM (SCID).
- Abuse of or dependence on alcohol or other substances within the past 3 months as determined by SCID, and confirmed by study physician interview.
- Alcohol use amounting to 15 or more drinks per week or drinking 5 or more drinks on one occasion during any given week.
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- High risk for suicide (e.g., active suicidal ideation (SI) and/or current/recent intent or plan) AND unable to be managed safely in the clinical trial (e.g., unwilling to be hospitalized). Urgent psychiatric referral will be made in these cases.
- Contraindication to venlafaxine extended release (XR) or BPN as determined by study physician including history of intolerance of either venlafaxine XR or BPN in the study target dosage range (venlafaxine XR at up to 300 mg/day; BPN at up to 2 mg/day).
- Inability to communicate in English (i.e., interview cannot be conducted without an interpreter; subject largely unable to understand questions and cannot respond in English).
- Non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview).
- Unstable medical illness, including delirium, uncontrolled diabetes mellitus, hypertension, or cerebrovascular or cardiovascular risk factors that are not under medical management. This will be determined based on information from the patient's personal physician and study physician's clinical judgment. Referral to the patient's personal physician or to a general practitioner will be made in these cases. Sodium and glucose levels done in the past 6 months are also reviewed before a subject begins study medication to determine if an illness is stable or uncontrolled. Individual lab parameters may deviate from normal without any associated pathophysiology or negative clinical affect; therefore we will follow the guide below before beginning starting any study medication.
- Sodium value of 135 but asymptomatic= consider to be normal and proceed without further testing.
- Sodium value of 134= repeat sodium. If value continues to be at 134 or higher and subject is asymptomatic, continue study participation but recheck sodium level after one week of exposure to study medication to confirm it has stayed stable.
- Sodium value of 133 or less= will evaluate subject's medication list to suggest possibly removing other medications which may be contributing to low sodium (in collaboration with their PCP), suggest fluid restriction and require repeat sodium that is normal range prior to commencing study.
- Glucose < 275 and asymptomatic= stable to proceed but will communicate value to PCP with participants permission.
- (see exclusion #17 for information on hepatic function lab parameters)
- Subjects taking psychotropic medications that cannot be safely tapered and discontinued prior to study initiation. The following exceptions are allowed if they have been taken at a stable dose for at least 4 weeks prior to study entry and there is not a plan to change the dose during the next 28 weeks: benzodiazepines up to 2 mg/d lorazepam equivalent; other sedative-hypnotics (e.g., zolpidem, zaleplon, eszopiclone); gabapentin if prescribed for non-psychiatric indication (e.g., neuropathy).
- History of opiate abuse or dependence.
- Severe pain, defined as >/= 7 on 0-10 numeric rating scale for pain.
- Concomitant use of strong or moderate CYP3A4 inhibitor (indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketonazole, nefazodone, saquinovir, telithromycin, aprepitant, erythromycin, fluconazole, grapefruit juice, verapamil, diltiazem)
- Refusal to stop all opioids (to avoid precipitating opioid withdrawal).
- Hepatic impairment- aspartate aminotransferase (AST) /alanine aminotransferase (ALT) > 1.5 times upper normal. If AST and ALT are within 1.5 times the upper limit, and subjects are asymptomatic, they will be considered medically stable to participate
- Estimated Glomerular Filtration Rate (GFR) < 20 ml/min.
- Inability/refusal to identify a person as an emergency contact.
- Pregnancy
- Contraindications to MRI
Trial locations and contacts
1 site in 1 country.
United States1 site
Western Psychiatric Institute and Clinic, University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
About this study
The purposes of this project are to examine the feasibility, safety, tolerability and clinical effect of low-dose buprenorphine as a novel treatment for late-life treatment-resistant depression and to develop preliminary data about mechanism of action.
Read the detailed description
Up to one half of older patients with major depression develop Late-Life Treatment Resistant Depression (LL-TRD). Consequences of LL-TRD include suicide, worsened medical conditions, increased caregiver burden, and higher all-cause mortality. The development and testing of novel-mechanism pharmacotherapies is a public health priority embraced by National Institute of Mental Health (NIMH). Among the neuropeptidergic transmitters, opioids are known to modulate mood, and this system is often altered in patients with major depression. Targeting the opiate system in LL-TRD may positively modulate a system in which there is age-associated imbalance between circulating opiates and the density and binding affinity of mu and kappa opiate receptors. Buprenorphine (BPN) is an antagonist at the kappa opiate receptor and a partial agonist at the mu opiate receptor. Either, or both, of these pharmacodynamic actions may underlie its putative antidepressant effects. Our research group has open pilot data from 15 older adults with prospectively demonstrated treatment resistance to venlafaxine who were exposed to low-dose BPN, suggesting a clinically meaningful antidepressant effect. In addition, since BPN: 1) is available in sublingual formulation and 2) has a favorable safety and pharmacokinetic profile, it is an attractive candidate to re-purpose as a molecule for LL-TRD. Thus, the overarching aims of this project are to examine the feasibility, safety, tolerability and clinical effect of low-dose BPN as a novel treatment for LL-TRD and to develop preliminary data about mechanism of action (MOA).
The overarching aims are to examine the feasibility, safety, and tolerability of buprenorphine (BPN) as a novel treatment for late-life treatment resistant depression (LL-TRD). This also involves using translational tools of modern neurobiology (fMRI) to rapidly obtain proof-of-concept support for further clinical development. Formal dosing schedules in the use of buprenorphine have yet to be thoroughly established. This study hopes to determine optimal dosing strategies to improve acceptability.
- Conditions
- Depression, Major Depressive Disorder
- Being tested
- Buprenorphine, Placebo
- Keywords
- Buprenorphine, Receptors, opioid, Receptors, opioid kappa and mu
- Medical subject headings
- Depression, Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BuprenorphineDrug
Also called suboxone, buprenex, temgesic, subutex
low-dose buprenorphine (range 0.2 mg/day -- 2.0 mg/day)
PlaceboDrug
matched placebo
| Study group | Role | What they receive |
|---|---|---|
| Buprenorphine | Experimental | Buprenorphine Receives: Drug: Buprenorphine |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Montgomery-Asberg Depression Rating Scale (MADRS)
Measure of depression severity, range of 0-60
We calculated the mean change in depression severity for both groups using baseline MADRS and week 8 MADRS scores.
Greater mean change represents better outcome.
Measured: baseline and 8 weeks
Secondary outcomes (1)
Brief Symptom Inventory--Anxiety Subscale (BSI)
Measure of Anxiety Theoretical Range 0-2.4 with lower numbers indicating a better outcome.
We calculated the mean change in anxiety for both groups using Phase 1 week 12 time point (baseline) and Phase 2 week 8 time point (final time point).
Measured: Baseline and 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2014 (estimated)
- Study startAug 2014
- Primary completionApr 2017
- Study completionFeb 2018
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.
- Other trials for DepressionStudies 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jordan F. Karp
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor-investigator, Jordan F. Karp, University of Pittsburgh
- Investigators
- Jordan F. Karp, M.D., Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02176291
- Sponsor's protocol ID
- PRO13120236
- Other IDs
- R34MH101371
- Acronym
- IRLGREY-B
- Status last verified
- Aug 2018
- First submitted
- 25 Jun 2014
- Last updated
- 29 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Incomplete Response in Late-Life Depression: Getting to Remission With Buprenorphine
- ClinicalTrials.gov ID
- NCT02176291
- Acronym / sponsor ID
- IRLGREY-B / PRO13120236
- Conditions
- Depression, Major Depressive Disorder
- Keywords
- Buprenorphine, Receptors, opioid, Receptors, opioid kappa and mu
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Jordan F. KarpUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Aug 2014
- Primary completion
- Apr 2017 (actual)
- Study completion
- Feb 2018 (actual)
- First posted
- 27 Jun 2014 (estimated)
- Results
- Posted 2 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purposes of this project are to examine the feasibility, safety, tolerability and clinical effect of low-dose buprenorphine as a novel treatment for late-life treatment-resistant depression and to develop preliminary data about mechanism of action.
Detailed description
Up to one half of older patients with major depression develop Late-Life Treatment Resistant Depression (LL-TRD). Consequences of LL-TRD include suicide, worsened medical conditions, increased caregiver burden, and higher all-cause mortality. The development and testing of novel-mechanism pharmacotherapies is a public health priority embraced by National Institute of Mental Health (NIMH). Among the neuropeptidergic transmitters, opioids are known to modulate mood, and this system is often altered in patients with major depression. Targeting the opiate system in LL-TRD may positively modulate a system in which there is age-associated imbalance between circulating opiates and the density and binding affinity of mu and kappa opiate receptors. Buprenorphine (BPN) is an antagonist at the kappa opiate receptor and a partial agonist at the mu opiate receptor. Either, or both, of these pharmacodynamic actions may underlie its putative antidepressant effects. Our research group has open pilot data from 15 older adults with prospectively demonstrated treatment resistance to venlafaxine who were exposed to low-dose BPN, suggesting a clinically meaningful antidepressant effect. In addition, since BPN: 1) is available in sublingual formulation and 2) has a favorable safety and pharmacokinetic profile, it is an attractive candidate to re-purpose as a molecule for LL-TRD. Thus, the overarching aims of this project are to examine the feasibility, safety, tolerability and clinical effect of low-dose BPN as a novel treatment for LL-TRD and to develop preliminary data about mechanism of action (MOA).
The overarching aims are to examine the feasibility, safety, and tolerability of buprenorphine (BPN) as a novel treatment for late-life treatment resistant depression (LL-TRD). This also involves using translational tools of modern neurobiology (fMRI) to rapidly obtain proof-of-concept support for further clinical development. Formal dosing schedules in the use of buprenorphine have yet to be thoroughly established. This study hopes to determine optimal dosing strategies to improve acceptability.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Buprenorphine | Experimental | Drug: BuprenorphineBuprenorphine |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age >/= to 50 years.
- Major depressive disorder (MDD), single or recurrent, as diagnosed by the Structured Clinical Interview for the DSM IV (SCID-IV).
- Montgomery-Åsberg Depression Rating Scale (MADRS) >/= to 15.
- Has or agrees to establish a clinical relationship with primary care physician (PCP).
- Availability of an informant (e.g., emergency contact).
Key exclusion criteria (26 listed)
- Inability to provide informed consent.
- Depressive symptoms not severe enough i.e.,Montgomery-Åsberg Depression Rating Scale ( MADRS) < 15 at the baseline assessments.
- Dementia, as defined by The Modified Mini-Mental State (3MS) examination < 84 and clinical evidence of dementia (e.g., memory impairment, executive dysfunction, agnosia, apraxia, aphasia, with functional impairment).
- Lifetime diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms, as diagnosed by the Structured Clinical Interview for DSM (SCID).
- Abuse of or dependence on alcohol or other substances within the past 3 months as determined by SCID, and confirmed by study physician interview.
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 |
|---|---|---|
| BuprenorphineAlso: suboxone, buprenex, temgesic, subutexlow-dose buprenorphine (range 0.2 mg/day -- 2.0 mg/day) | Drug | Buprenorphine |
| Placebomatched placebo | Drug | Placebo |
Primary outcome
Montgomery-Asberg Depression Rating Scale (MADRS)
Time frame: baseline and 8 weeks
Measure of depression severity, range of 0-60 We calculated the mean change in depression severity for both groups using baseline MADRS and week 8 MADRS scores. Greater mean change represents better outcome.
1 secondary outcome
Brief Symptom Inventory--Anxiety Subscale (BSI)
Time frame: Baseline and 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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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.
Jordan F. Karp, M.D. principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Buprenorphine in people with Depression and Major Depressive Disorder, run by Jordan F. Karp 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 26 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 29 Aug 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 2 Jul 2018). 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?
Montgomery-Asberg Depression Rating Scale (MADRS) (time frame: baseline and 8 weeks). 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 29 Aug 2018.