Clinical trial NCT03646058: Add-on Buprenorphine At Analgesic Doses for the Treatment of Severe Suicidal Ideas During a Major Depressive Episode
Official title: Add-on Buprenorphine At Analgesic Doses for the Treatment of Severe Suicidal Ideas During a Major Depressive Episode
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Suicidal Ideation
Major Depressive Episode
Keywords: Treatment
Suicidal ideas
Depression
Buprenorphine
Opioid agonist
Mental pain
Lead sponsor: Centre Hospitalier Universitaire de Nīmes
Sponsor class: OTHER
First posted: 2018-08-24
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study aims at investigating if adjunctive buprenorphine at low dose to treatment as usual is effective in reducing severe suicidal ideas in major depressive episode, and at determining the most effective dose.

Detailed description: Participants will be randomized to two doses of buprenorphine (0.4mg and 0.8mg) or placebo. The duration of treatment will be 21 days with 7 days withdrawal period. Two follow-up phone calls at 3 and 6 months will investigate occurence of suicidal behavior.

The main outcome will be changes in suicidal ideas levels during the first week.

Secondary outcomes will be changes in suicidal ideas during the following 21 days, changes in depression and psychological pain levels over the first 28 days, dropout rates, reasons and occurence of side effects over the first 28 days, withdrawal symptoms dung the withdrawal period, changes in neuropsychological and neuroimaging measures between Day 0 and Day 28.

Blood and stool samples will be collected at 4 time points and stored in a biobank for future analyses.

Eligibility criteria: Inclusion Criteria:

* The patient has been correctly informed.
* The patient must have given his/her informed and signed the consent form.
* The patient must be insured or beneficiary of a health insurance plan.
* The patient is at least 18 years old and 65 years old at the most.
* The patient is hospitalized or followed in consultation.
* The patient has a current major depressive episode without psychotic features according to the criteria of the "Diagnostic and Statistical Manual of Mental Disorders"
* The patient has a score \> 20 of the "Montgomery-Asberg Depression Rating Scale".
* The patient has a current Scale for Suicidal Ideation (SSI) score \> 8.

Exclusion Criteria:

* The patient is participating in another interventional trial;
* The patient is in an exclusion period determined by a previous study;
* The patient is under judicial protection, or is an adult under guardianship;
* The patient is under compulsory admission;
* The patient refuses to sign the consent;
* it is impossible to correctly inform the patient.
* The patient is pregnant or breastfeeding.
* The patient suffers from schizophrenia;
* The patient suffered from moderate to severe alcohol use disorder or substance use disorder (except tobacco and caffeine) over the last 12 months according to DSM-5 criteria ;
* The patient currently suffers from severe and/or unstable medical condition (including severe respiratory or hepatic insufficiency) or a painful medical condition;
* The patient has a current known sleep apnea.
* The patient currently takes analgesic treatment (including Nonsteroidal anti-inflammatory drug and paracetamol);
* The patient currently takes central nervous depressant drugs at sedative doses (based on the investigator's assessment), including benzodiazepines, antihistamines, and sedative antipsychotics;
* The patient currently takes major CYP3A4 Inhibitors and inducers;
* The patient currently takes has received Electroconvulsivotherapy over the last 3 months.

Primary outcomes:
measure: Changes in Beck Scale for Suicidal Ideation (SSI) scores from Day 0 to 7
timeFrame: 7 days
Secondary outcomes:
measure: Changes in Beck Scale for Suicidal Ideation (SSI) scores
timeFrame: Day 8 to day 28
measure: Changes in Beck Depression Inventory II (BDI-II) scores from Day 0 to 28
timeFrame: 28 days
measure: Changes in Montgomery-Asberg Depression Rating Scale (MADRS) from Day 0 to 28
timeFrame: 28 days
measure: Changes in Physical and Psychological Pain - Visual Analog Scale (PPP-VAS) scores from Day 0 to 28
timeFrame: 28 days
measure: Reasons for discontinuing treatment over the first 28 days
timeFrame: 28 days
measure: Side effects over the first 28 days
timeFrame: 28 days
measure: Withdrawal symptoms
timeFrame: Day 22 to day 28
measure: Occurence of a suicide attempt during the whole study
timeFrame: 180 days
measure: Changes in Iowa Gambling Task (IGT) scores between Day 0 and 28
timeFrame: 28 days
measure: Changes in modified Stroop test scores between Day 0 and 28
timeFrame: 28 days
measure: Changes in verbal fluency test scores between Day 0 and 28
timeFrame: 28 days
measure: Changes in N-Back test scores between Day 0 and 28
timeFrame: 28 days
measure: Changes in Go/No-Go test between Day 0 and 28
timeFrame: 28 days
measure: Changes in Trail Making Test (TMT) scores between Day 0 and 28
timeFrame: 28 days
measure: Changes in Implicit Association Test (IAT) scores between Day 0 and 28
timeFrame: 28 days
measure: Changes in Magnetic Resonance Imaging (MRI) T1 measures between Day 0 and 28
timeFrame: 28 days
measure: Changes in Magnetic Resonance Imaging (MRI) T2 measures between Day 0 and 28
timeFrame: 28 days
measure: Changes in Magnetic Resonance Imaging (MRI) Diffusion Tensor Imaging (DTI) measures between Day 0 and 28
timeFrame: 28 days
measure: Changes in Magnetic Resonance Imaging (MRI) Resting State (RS) measures between Day 0 and 28
timeFrame: 28 days
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Ch Perrens
city: Le Kremlin-Bicêtre
country: France
facility: CHU Bicêtre
city: Lyon
country: France
facility: Hospices Civils de Lyon
city: Nantes
country: France
facility: CAPPA Jacques PREVERT
city: Nîmes
country: France
facility: CHU Nîmes
city: Paris
country: France
facility: CH Sainte-Anne
city: Poitiers
country: France
facility: CH Henri Laborit
city: Toulouse
country: France
facility: Chu Toulouse Hopital Purpan
city: Tours
country: France
facility: CHU de Tours
Study officials:
affiliation: Hôpital Sainte-Anne
name: Fabrice Jollant, MD
role: PRINCIPAL_INVESTIGATOR
References: