NAlmefene versus placebo in addition to treatment as usual on craving in Behavioural Addictions (NABAb)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Nantes

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Behavior and Behavior Mechanisms [F01]

Trial duration

31 Mar 2023 → ongoing

Decision date (initial)

2022-08-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To assess the efficacy of nalmefene versus placebo as an add-on to treatment as usual for reducing intensity of craving episodes in patients with Behavioural Addictions (Gambling Desorder, Sexual Addiction, Food Addiction), at the end of treatment at maximum dosage tolerated.

Secondary objectives 8

1. Compare the two groups (Placebo vs Nalmefene) on the efficacy of nalmefene for reducing frequency and duration of craving episodes at end of treatment.
2. Compare the two groups (Placebo vs Nalmefene) on the efficacy of nalmefene for reducing craving intensity, frequency and duration of craving episodes at 4 weeks after the end of treatment.
3. Compare the two groups (Placebo vs Nalmefene) on the efficacy of nalmefene for reducing BAs episodes (frequency, duration and intensity) at end of treatment and 4 weeks after.
4. Compare the two groups (Placebo vs Nalmefene) on the efficacy of nalmefene on overall clinical improvement, as perceived by the clinician.
5. Compare the two groups (Placebo vs Nalmefene) on the impact of nalmefene on co-use of psychoactive substances (including nicotine) and daily life behaviors of interest (gambling, sex, food).
6. Compare the two groups (Placebo vs Nalmefene) on the overall safety of nalmefene, at the two dosages used (18 mg/d and then 36 mg/d).
7. Investigate the link between efficacy of treatment and polymorphisms in the genes involved in pharmacodynamics (coding for the 3 opioid receptors [OPRM1, OPRD1 and OPRK1] and the 5 dopaminergic receptors) and pharmacokinetics (proteins involved in the metabolism of nalmefene, especially the UGT 2B7 enzyme, or in its availability, especially P-gP) of nalmefene.
8. Characterize the profiles of responders/non-responders to treatment with Nalmefene, in terms of the sociodemographic and clinical (especially psychiatric and addictive co-morbidities) characteristics.

Conditions and MedDRA coding

Patients with gambling disorder or sexual addiction or food addiction

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Males and females ≥ 18 years old
2. Patient already in care or newly initiating care in Addictology departments for a behavioural addiction, diagnosed with current : - Gambling disorder / - Food addiction / - Or Sexual addiction.
3. Able to regularly assess and report their craving episodes on a weekly diary
4. Who provide their written informed consent
5. Affiliated with French social security system or beneficiary from such system
6. Having presented at least one episode of craving with an intensity ≥ 4/10 at the NRS during the week prior to inclusion
7. Women must meet one of the following criteria at the time of inclusion: use adequate contraceptive measures as recommended by the CTFG, and have a negative pregnancy test prior to receiving the first dose of study drug; or be post-menopausal (over 50 years of age with amenorrhea for at least 12 months after discontinuation of all exogenous hormonal therapy); or (if under 50 years of age) have been amenorrheic for at least 12 months after discontinuation of exogenous hormonal therapy and with luteinizing hormone and follicle stimulating hormone levels corresponding to post-menopausal levels; or have undergone irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy.

Exclusion criteria 14

1. Being currently treated by another anti-craving drug that have been already tested for craving reduction in BAs (naltrexone, acamprosate, baclofène, topiramate, bupropion, N-acetyl-cystéine, disulfiram, etc.)
2. Pregnancy (attested by a pregnancy urinary test for women of childbearing age) or breastfeeding woman
3. Trusteeship
4. Major cognitive impairment
5. Not fluent in French
6. Participation to another interventional study during the last month or expected participation to another interventional study during participation to the NABAB study
7. Presenting a contraindication for the use of nalmefene (listed in the SmPC) : - Known hypersensitivity to the active substance or to any of the excipients. In particular, intolerance to galactose or deficiency in Lapp lactase or glucose-galactose malabsorption (rare hereditary diseases) / - Treatment by opioid agonists (full or partial) (opioid pain relievers, opioid substitution drugs) / - Recent history of opioid dependence or current opioid dependence / - Current symptoms of the acute opioid withdrawal syndrome / - Suspected recent consumption of opioid (necessity to consider the half-life) / - Severe hepatic impairment (Child-Pugh stage B or C) / - Severe renal impairment (estimated glomerular filtration rate [TFGe] <30 mL/min/1.73 m2 ) / - History of recent acute alcohol withdrawal syndrome (including hallucinations, convulsions and delirium tremens).
8. Predictable opioid treatment during the study period
9. Unstable psychiatric disorders (meaning disorders for which the treatment was modified since less than a month (corresponding to the instauration of a new treatment, or the increase in dosage of a treatment already being taken)), including severe risk of suicide (i.e. necessity to engage specific medication or hospitalization; psychotropic medication engaged since less than 1 month; absence of improvement after one month of medication) (because nalmefene has not been studied in patients with unstable psychiatric disorders). Patients with a food addiction diagnosed with eating disorders marked by the presence of binge eating can be included
10. Anorexia nervosa-restricting type (because food addiction concept is poorly established among patients with AN-R, who do not have binge eating episodes induced by craving)
11. Extreme leanness (body mass index < 16.5) (because loss of appetite and/or weight loss are frequent adverse effects of nalmefene)
12. Current treatment with potent inhibitor drugs of the UGT2B7 (UDP-Glucuronosyltransferase-2B7); for example: diclofenac, fluconazole, medroxyprogesterone acetate, meclofenamic acid
13. Current treatment with UGT inducing drugs; for example: dexamethasone, phenobarbital, rifampicin, omeprazole
14. Inability to indicate the time of day of the most intense craving episode (because this information will determine the time of day the treatment should be taken)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Variation of averaged intensity of craving episodes between start (during the week preceding initiation of treatment) and end (during the week preceding end of treatment) of treatment. Each craving episode will be reported by the patient on a weekly diary, with intensity assessed through a Numerical Rating Scale (NRS).

Secondary endpoints 8

1. Variation of averaged weekly frequency (number of episodes) and duration (cumulative duration of all episodes) of craving episodes between start and end of treatment.
2. Variation of averaged weekly intensity, frequency and duration of craving episodes between start of treatment and 4 weeks after the end of treatment.
3. Variation of averaged weekly frequency, duration and intensity (assessed through a NRS) of the BA episodes: (i) between start and end of treatment and (ii) between start of treatment and 4 weeks after the end of treatment.
4. Overall clinical improvement, assessed though the Clinical Global Impression – Improvement (CGI-I) scale and the GGI – Efficacy Index (CGI-EI).
5. Variation of averaged weekly use of psychoactive substances (including nicotine) and daily life behaviors of interest (gambling, sex, food) between start of treatment and 4 weeks after the end of treatment.
6. Number, type and severity of self-reported adverse side effects, during either weeks of treatment at a dosage of 18 mg/d or 36 mg/d.
7. Mutation(s) associated with non-response to nalmefene treatment; such mutations will be identified using a NGS (Next-Generation Sequencing) panel.
8. Sociodemographic, medical and clinical data, especially psychiatric and addictive co-morbidities assessed with the Mini International Neuropsychiatric Interview – Simplified (MINI-S) and the age of the BA

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Nantes

Sponsor organisation

Centre Hospitalier Universitaire De Nantes

Address

5 Allee De L Ile Gloriette, Cs 69301 Cs 69301

City

Nantes Cedex 1

Postcode

44093

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Nantes

Contact name

Marie GRALL-BRONNEC

Public contact point

Organisation

Centre Hospitalier Universitaire De Nantes

Contact name

Marie GRALL-BRONNEC

Locations

1 EU/EEA country · 13 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 6 files

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

Application history

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