Add-on Buprenorphine at Analgesic Doses for the Treatment of Severe Suicidal Ideas During a Major Depressive Episode

Suicidal Ideation Clinical Trial

— BUPRIS  

Official title:

Add-on Buprenorphine at Analgesic Doses for the Treatment of Severe Suicidal Ideas During a Major Depressive Episode

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03646058
• Other study ID #: PHRC-N/2017/FJ-01
• Status: Recruiting
• Phase: Phase 3
• Start date: October 10, 2021
• Est. completion date: January 2026

Study information

• Verified date: February 2024
• Source: Centre Hospitalier Universitaire de Nimes
• Contact: Fabrice Jollant, MD
• Phone: +33(0)1 45 65 85 72
• Email: fabrice.jollant[@]parisdescartes.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: January 2026
• Est. primary completion date: October 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Episode
• Suicidal Ideation

Intervention

Drug:
• Buprenorphine
Buprenorphine, 0.4mg pills, sublingual
• Placebo
Placebo pills, sublingual, specifically made to mimick buprenorphine pills

Locations

Country	Name	City	State
France	Ch Perrens	Bordeaux
France	CHU Grenoble Alpes	La Tronche
France	CHU Bicêtre	Le Kremlin-Bicêtre
France	Hospices Civils de Lyon	Lyon
France	CAPPA Jacques PREVERT	Nantes
France	CHU Nîmes	Nîmes
France	CH Sainte-Anne	Paris
France	CH Henri Laborit	Poitiers
France	Chu Toulouse Hopital Purpan	Toulouse
France	CHU de Tours	Tours

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Nimes

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in Beck Scale for Suicidal Ideation (SSI) scores from Day 0 to 7	Clinician-based questionnaire measuring level of suicidal ideas over the last 7 days; 21 items scored 0 to 2; total score ranges from 0 to 38 (last 2 items not counted), higher scores mean more intense suicidal ideas.	7 days
Secondary	Changes in Beck Scale for Suicidal Ideation (SSI) scores	Clinician-based questionnaire measuring level of suicidal ideas over the last 7 days; 21 items scored 0 to 2; total score ranges from 0 to 38 (last 2 items not counted); higher scores mean more intense suicidal ideas.	Day 8 to day 28
Secondary	Changes in Beck Depression Inventory II (BDI-II) scores from Day 0 to 28	Self questionnaire measuring depression level over the last 7 days; 13 items scored 0 to 3, with the total score ranging from 0 to 39; higher scores mean higher level of depression.	28 days
Secondary	Changes in Montgomery-Asberg Depression Rating Scale (MADRS) from Day 0 to 28	Clinician-based questionnaire measuring the level of depression of the last 7 days; 10 items score 0 to 6, with the total scores ranging fron 0 to 60; Higher scores mean higher level of depression.	28 days
Secondary	Changes in Physical and Psychological Pain - Visual Analog Scale (PPP-VAS) scores from Day 0 to 28	Visual Analog Scale measuring physical then psychological pain over 3 periods each (current, worst over the last 7 days, mean over the last 7 days); 6 dimensions in total; each dimension is scored from 0 (no pain) to 10 (maximal pain).	28 days
Secondary	Reasons for discontinuing treatment over the first 28 days	Patient's self-report; measurement will be the overall (over 28 days) incidence for each event reported.	28 days
Secondary	Side effects over the first 28 days	Patient's self-report; measurement will be the overall (over 28 days) incidence for each event reported.	28 days
Secondary	Withdrawal symptoms	Patient's self-report; measurement will be the incidence of any withdrawal symptom during the withdrawal phase.	Day 22 to day 28
Secondary	Occurence of a suicide attempt during the whole study	Interview based; measurement will be the incidence of any suicide attempt between Day 0 and 28, between Day 29 and 90, and between Day 90 and 180.	180 days
Secondary	Changes in Iowa Gambling Task (IGT) scores between Day 0 and 28	Computerized test measuring decision-making; scores are the difference between advantageous and disadvantageous choices; scores range from -100 to + 100, higher scores means better performance	28 days
Secondary	Changes in modified Stroop test scores between Day 0 and 28	Classical Stroop test modified with suicide-related words to measure specific attention bias; scores are the number of errors and total reaction time; higher scores mean worse performance	28 days
Secondary	Changes in verbal fluency test scores between Day 0 and 28	Classical test measuring verbal fluency skills for semantic and phonological categories; Patients are instructed to give as many words as possible for a given category then for words starting with a given letter, within a 1 minute time frame; Scores are the number of correct words; higher scores mean higher performance	28 days
Secondary	Changes in N-Back test scores between Day 0 and 28	Classical test of working memory using letters; scores are the number of words correctly identified for each level of recall (0 to 2 back); higher scores mean better performance; also, the number of omission and commission errors.	28 days
Secondary	Changes in Go/No-Go test between Day 0 and 28	Classical test of cognitive inhibition, letter version; scores are the number of omission and commission errors (higher scores mean worse performance) and reaction times (higher scores mean better performance)	28 days
Secondary	Changes in Trail Making Test (TMT) scores between Day 0 and 28	Classical test of planning abilities; scores are the difference between the time to complete parts B and A of the test; Higher scores mean worse performance.	28 days
Secondary	Changes in Implicit Association Test (IAT) scores between Day 0 and 28	IAT version adapted for suicide/death; scores are the measure of reaction times in the association between suicide/death words and me/myself words; lower scores mean higher association.	28 days
Secondary	Changes in Magnetic Resonance Imaging (MRI) T1 measures between Day 0 and 28	Brain structural MRI-T1 sequence measured at Day 0 and Day 28 (5 minutes)	28 days
Secondary	Changes in Magnetic Resonance Imaging (MRI) T2 measures between Day 0 and 28	Brain structural MRI-T2 sequence measured at Day 0 and Day 28 (5 minutes)	28 days
Secondary	Changes in Magnetic Resonance Imaging (MRI) Diffusion Tensor Imaging (DTI) measures between Day 0 and 28	Brain Diffusion Tensor Imaging (DTI) sequence measured at Day 0 and Day 28 (20 minutes)	28 days
Secondary	Changes in Magnetic Resonance Imaging (MRI) Resting State (RS) measures between Day 0 and 28	Brain functional Resting State (RS) sequence measured at Day 0 and Day 28 (15 minutes)	28 days