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

Primary Purpose

Suicidal Ideation, Major Depressive Episode

Status
Recruiting
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Buprenorphine
Placebo
Sponsored by
Centre Hospitalier Universitaire de Nīmes
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Suicidal Ideation focused on measuring Treatment, Suicidal ideas, Depression, Buprenorphine, Opioid agonist, Mental pain

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 has a lifetime history of substance use disorder (except tobacco and caffeine), moderate to severe, according to criteria of the "Diagnostic and Statistical Manual of Mental Disorders";
  • 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.

Sites / Locations

  • Ch Perrens
  • CHU Grenoble Alpes
  • CHU BicêtreRecruiting
  • Hospices Civils de LyonRecruiting
  • CAPPA Jacques PREVERTRecruiting
  • CHU NîmesRecruiting
  • CH Sainte-AnneRecruiting
  • CH Henri LaboritRecruiting
  • CHU de ToursRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Experimental

Experimental

Arm Label

Placebo

0.4mg buprenorphine

0.8mg buprenorphine

Arm Description

2 placebo pills sublingual during 28 days

1 pill of 0.4 mg buprenorphine + 1 placebo pill per day for 21 days, then 2 placebo pills per day for 1 week, all sublingual.

1 pill of 0.4 mg buprenorphine + 1 placebo pill per day for 3 days, then 2 pills of 0.4mg buprenorphine per day for 18 days, then 1 pill of 0.4 mg + 1 placebo pill per day for 3 days, then 2 placebo pills per day for 4 days, all sublingual.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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).
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.
Side effects over the first 28 days
Patient's self-report; measurement will be the overall (over 28 days) incidence for each event reported.
Withdrawal symptoms
Patient's self-report; measurement will be the incidence of any withdrawal symptom during the withdrawal phase.
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.
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
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
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
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.
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)
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.
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.
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)
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)
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)
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)

Full Information

First Posted
August 16, 2018
Last Updated
June 22, 2023
Sponsor
Centre Hospitalier Universitaire de Nīmes
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1. Study Identification

Unique Protocol Identification Number
NCT03646058
Brief Title
Add-on Buprenorphine at Analgesic Doses for the Treatment of Severe Suicidal Ideas During a Major Depressive Episode
Acronym
BUPRIS
Official Title
Add-on Buprenorphine at Analgesic Doses for the Treatment of Severe Suicidal Ideas During a Major Depressive Episode
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 10, 2021 (Actual)
Primary Completion Date
October 2025 (Anticipated)
Study Completion Date
January 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Hospitalier Universitaire de Nīmes

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Suicidal Ideation, Major Depressive Episode
Keywords
Treatment, Suicidal ideas, Depression, Buprenorphine, Opioid agonist, Mental pain

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
180 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
2 placebo pills sublingual during 28 days
Arm Title
0.4mg buprenorphine
Arm Type
Experimental
Arm Description
1 pill of 0.4 mg buprenorphine + 1 placebo pill per day for 21 days, then 2 placebo pills per day for 1 week, all sublingual.
Arm Title
0.8mg buprenorphine
Arm Type
Experimental
Arm Description
1 pill of 0.4 mg buprenorphine + 1 placebo pill per day for 3 days, then 2 pills of 0.4mg buprenorphine per day for 18 days, then 1 pill of 0.4 mg + 1 placebo pill per day for 3 days, then 2 placebo pills per day for 4 days, all sublingual.
Intervention Type
Drug
Intervention Name(s)
Buprenorphine
Other Intervention Name(s)
Temgesic
Intervention Description
Buprenorphine, 0.4mg pills, sublingual
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo pills, sublingual, specifically made to mimick buprenorphine pills
Primary Outcome Measure Information:
Title
Changes in Beck Scale for Suicidal Ideation (SSI) scores from Day 0 to 7
Description
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.
Time Frame
7 days
Secondary Outcome Measure Information:
Title
Changes in Beck Scale for Suicidal Ideation (SSI) scores
Description
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.
Time Frame
Day 8 to day 28
Title
Changes in Beck Depression Inventory II (BDI-II) scores from Day 0 to 28
Description
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.
Time Frame
28 days
Title
Changes in Montgomery-Asberg Depression Rating Scale (MADRS) from Day 0 to 28
Description
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.
Time Frame
28 days
Title
Changes in Physical and Psychological Pain - Visual Analog Scale (PPP-VAS) scores from Day 0 to 28
Description
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).
Time Frame
28 days
Title
Reasons for discontinuing treatment over the first 28 days
Description
Patient's self-report; measurement will be the overall (over 28 days) incidence for each event reported.
Time Frame
28 days
Title
Side effects over the first 28 days
Description
Patient's self-report; measurement will be the overall (over 28 days) incidence for each event reported.
Time Frame
28 days
Title
Withdrawal symptoms
Description
Patient's self-report; measurement will be the incidence of any withdrawal symptom during the withdrawal phase.
Time Frame
Day 22 to day 28
Title
Occurence of a suicide attempt during the whole study
Description
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.
Time Frame
180 days
Title
Changes in Iowa Gambling Task (IGT) scores between Day 0 and 28
Description
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
Time Frame
28 days
Title
Changes in modified Stroop test scores between Day 0 and 28
Description
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
Time Frame
28 days
Title
Changes in verbal fluency test scores between Day 0 and 28
Description
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
Time Frame
28 days
Title
Changes in N-Back test scores between Day 0 and 28
Description
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.
Time Frame
28 days
Title
Changes in Go/No-Go test between Day 0 and 28
Description
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)
Time Frame
28 days
Title
Changes in Trail Making Test (TMT) scores between Day 0 and 28
Description
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.
Time Frame
28 days
Title
Changes in Implicit Association Test (IAT) scores between Day 0 and 28
Description
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.
Time Frame
28 days
Title
Changes in Magnetic Resonance Imaging (MRI) T1 measures between Day 0 and 28
Description
Brain structural MRI-T1 sequence measured at Day 0 and Day 28 (5 minutes)
Time Frame
28 days
Title
Changes in Magnetic Resonance Imaging (MRI) T2 measures between Day 0 and 28
Description
Brain structural MRI-T2 sequence measured at Day 0 and Day 28 (5 minutes)
Time Frame
28 days
Title
Changes in Magnetic Resonance Imaging (MRI) Diffusion Tensor Imaging (DTI) measures between Day 0 and 28
Description
Brain Diffusion Tensor Imaging (DTI) sequence measured at Day 0 and Day 28 (20 minutes)
Time Frame
28 days
Title
Changes in Magnetic Resonance Imaging (MRI) Resting State (RS) measures between Day 0 and 28
Description
Brain functional Resting State (RS) sequence measured at Day 0 and Day 28 (15 minutes)
Time Frame
28 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Fabrice Jollant, MD
Phone
+33(0)1 45 65 85 72
Email
fabrice.jollant@parisdescartes.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fabrice Jollant, MD
Organizational Affiliation
Hôpital Sainte-Anne
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ch Perrens
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
TOURNIER MARIE, PUPH
Phone
05 56 56 17 71
Email
mtournier@ch-perrens.fr
Facility Name
CHU Grenoble Alpes
City
La Tronche
ZIP/Postal Code
38700
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mircea Polosan, MD
Phone
+33(0)4 76 76 87 10
Email
MPolosan@chu-grenoble.fr
Facility Name
CHU Bicêtre
City
Le Kremlin-Bicêtre
ZIP/Postal Code
94270
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Emmanuelle Corruble, MD
Phone
+33(0)1 45 21 25 24
Email
emmanuelle.corruble@bct.aphp.fr
Facility Name
Hospices Civils de Lyon
City
Lyon
ZIP/Postal Code
69003
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Emmanuel Poulet, MD
Phone
+33(0)4 72 11 00 09
Email
emmanuel.poulet@chu-lyon.fr
Facility Name
CAPPA Jacques PREVERT
City
Nantes
ZIP/Postal Code
44000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anne Sauvaget, MD
Phone
+33(0)2.40.08.47.95
Email
anne.sauvaget@chu-nantes.fr
Facility Name
CHU Nîmes
City
Nîmes
ZIP/Postal Code
30029
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mocrane Abbar, MD
Phone
+33 (0)4.66.68.42.36
Email
m-abbar@chu-nimes.fr
First Name & Middle Initial & Last Name & Degree
Jorge Lopez Castroman, MD
First Name & Middle Initial & Last Name & Degree
Ismaël Conegero, MD
First Name & Middle Initial & Last Name & Degree
Fabricio Pereira
Facility Name
CH Sainte-Anne
City
Paris
ZIP/Postal Code
75674
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fabrice Jollant, MD
Phone
+33 (0)1 45 55 65 92
Email
fabrice.jollant@parisdescartes.fr
Facility Name
CH Henri Laborit
City
Poitiers
ZIP/Postal Code
86021
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nemat Jaafari, MD
Phone
+33(0)5 16 52 61 18
Email
nemat.jaafari@ch-poitiers.fr
Facility Name
CHU de Tours
City
Tours
ZIP/Postal Code
37540
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wissam El-Hage, MD
Phone
+33(0)2 47 47 80 43
Email
wissam.elhage@univ-tours.fr

12. IPD Sharing Statement

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

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