Add-on buprenorphine at analgesic doses for the treatment of severe suicidal ideas during a major depressive episode

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Nimes

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

1 Jul 2021 → ongoing

Decision date (initial)

2024-05-07

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

DGOS / CHU de Nimes

External identifiers

EU CT number

2024-512445-17-00

EudraCT number

2018-003816-38

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

To show a significant effect of buprenorphine vs. placebo for the treatment of suicidal ideas at D7, and assess the most effective dosage (0.8mg vs. 0.4mg) of buprenorphine.

Secondary objectives 10

1. To show maintenance of a significant effect of buprenorphine on suicidal ideas from D0 to D42.
2. To show a significant effect of buprenorphine on psychological pain from D0 to D14 and a mediating effect of psychological pain in the relationship between buprenorphine and suicidal ideas.
3. To determine the effect of buprenorphine on the depressive syndrome in general (excluding suicidal ideas and psychological pain) from D0 to D14.
4. To determine the treatment arm with the lowest number of discontinuations for inefficacy according to the patient from D0 to D14.
5. To determine the number of suicide attempts or completed suicides during follow-up from D0 to D90.
6. To determine the dose of buprenorphine with the best tolerance profile from D0 to D14.
7. To determine the frequency of withdrawal symptoms from D14 to D21 for each dose.
8. To identify the physiological mechanisms underlying psychological pain and suicidal ideation, the biological mechanisms of response to buprenorphine treatment, and the predictive factors of response to buprenorphine by Neuropsychological processes;
9. To identify the physiological mechanisms underlying psychological pain and suicidal ideation, the biological mechanisms of response to buprenorphine treatment, and the predictive factors of response to buprenorphine by Brain processes (both structural and functional alterations);
10. Biochemical processes (epigenetic markers, inflammatory markers, intestinal microbiota). We will create a biobank in anticipation of ancillary studies (additional funding will be sought for these analyses).

Conditions and MedDRA coding

mental disorders

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. The patient is a man or a woman aged at least 18 years old and 65 years old at the most.
2. The patient is hospitalized
3. The patient suffers from a current major depressive episode without psychotic features according to DSM-5 criteria and a Montgomery-Asberg Depression Rating Scale (MADRS) score > 20, as part of a bipolar or major depressive disorder.
4. The patient has a current Scale for Suicidal Ideation (SSI) score > 8.
5. The patient must have given his/her informed and signed consent.
6. The patient must be insured or beneficiary of a health insurance plan.

Exclusion criteria 25

1. The patient is participating in another interventional trial;
2. The patient is in an exclusion period determined by a previous study;
3. The patient is under judicial protection, or is an adult under guardianship;
4. The patient is under compulsory admission;
5. The patient refuses to sign the consent
6. it is impossible to correctly inform the patient.
7. The patient actively followed in consultation
8. The patient is pregnant or breastfeeding.
9. The patient suffers from schizophrenia
10. 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
11. The patient has received Electroconvulsivotherapy (ECT) over the last 3 months.
12. The patient currently suffers from severe and/or unstable medical condition (including severe respiratory, renal or hepatic insufficiency) or a painful medical condition;
13. The patient has a current known sleep apnea.
14. The patient has a severe renal impairment
15. The patient currently takes analgesic treatment (incl. NSAID and paracetamol);
16. The patient takes central nervous depressant drugs at sedative doses (based on the investigator’s assessment), including sedative antidepressants, benzodiazepines, antihistamines, and sedative antipsychotics;
17. The patient receives major CYP3A4 Inhibitors and inducers medication;
18. Contra-indications mentioned for in SCP (Summary of product characteristics) of buprénorphine.
19. Use of alcohol or medication containing alcohol
20. Patient receives a Monoamine Oxydase Inhibitor (MAOI) antidepressant
21. Contra-indications mentioned in SCP (Summary of product characteristics) of buprénorphine and in particular Hypersensitivity to the active substance or to any of the excipients mentioned in section 6.1. of the SCP
22. Contra-indications mentioned in SCP (Summary of product characteristics) of buprénorphine and in particular Severe respiratory insufficiency (Altered respiratory function due to any medical condition (e.g chronic obstructive pulmonary disease, asthma, hypoxia, hypercapnia, pre-exisiting respiratory depression)
23. Contra-indications mentioned in SCP (Summary of product characteristics) of buprénorphine and in particular Severe hepatic insufficiency
24. Contra-indications mentioned in SCP (Summary of product characteristics) of buprénorphine and in particular Acute alcohol poisoning or delirium tremens.
25. Contra-indications mentioned in SCP (Summary of product characteristics) of buprénorphine and in particular Combination with méthadone, level III morphinic painkillers, naltrexone, and nalméfène.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Scores on the Scale for Suicidal Ideation (SSI) at Day 7 for the last 7 days

Secondary endpoints 10

1. Score on the SSI from D7 to 42 for the last 7 days (except at D2 = for the last 2 days)
2. Psychological pain evaluation by a Visual Analog Scale (PPP-VAS) from D0 to D42 (current and for the last 7 days, except at D2 = for the last 2 days)
3. Scores at the Beck Depression Inventory (BDI-II) and Montgomery-Asberg Depression Rating Scale (MADRS) after excluding the suicidal ideation items, for the last 7 days.
4. Reports of the reasons for discontinuing treatment
5. Reports of suicide attempts and suicide completion after the treatment phase
6. Reports of side effects
7. Reports of withdrawal symptoms
8. Scores at neuropsychological tests
9. 3T Magnetic Resonance Imaging measurements
10. Blood and stool samples collection to create a biobank

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Nimes

Sponsor organisation

Centre Hospitalier Universitaire De Nimes

Address

Place Du Professeur Robert Debre

City

Nimes Cedex 9

Postcode

30029

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Nimes

Contact name

LEONIE GAZEL

Public contact point

Organisation

Centre Hospitalier Universitaire De Nimes

Contact name

LEONIE GAZEL

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications