NAlmefene Versus Placebo in Addition to Treatment as Usual on Craving in Behavioural Addictions

NCT05540288 | Recruiting Phase 3 DMC

• 1 other identifier: RC21_0336
• Study Type: interventional
• Target: 266
• Locations: 1 country
• Sites: 13

Brief Summary

Behavioural addictions (BAs) \[gambling disorder (GD), food addiction (FA), sexual addiction (SA)\] may lead to disastrous consequences. They are often associated with other addictive or psychiatric disorders, and high rates of suicide attempts. Epidemiological studies report prevalence reaching 2.7% for GD, 5% for SA, and up to 7.9% for FA. Many similarities have been highlighted between BAs, as well as with substance use disorders. One core clinical similarity between those disorders is craving (uncontrollable urge to engage in rewarding behaviours), which has been consistently associated with diminished control over the behaviour and relapse. At present, no pharmacological treatment has been approved for BAs, but several medications have been tested. Among them, two opioid receptor antagonists - naltrexone and nalmefene - appear the most promising. By decreasing dopamine neurotransmission in the reward circuitry, they reduce both excitement for rewarding behaviours and craving. Compared to naltrexone, nalmefene seems to have a better safety. To date, no study investigated the efficacy of nalmefene as a pan-addiction treatment for BAs. Two clinical trials have demonstrated its efficacy for the treatment of GD, but no clinical trial was conducted for FA and SA. The investigators hypothesise that nalmefene (36 mg/d), compared to a placebo, can have a therapeutic effect as an add-on to usual treatment for decreasing craving in several BAs.

Conditions

Behavioural Addiction

Keywords

Nalmefene; Craving; Behavioural addiction; Gambling disorder; Food addiction; Sexual addiction

Outcome Measures

Primary Outcomes (1)

• Variation of averaged intensity of craving episodes between start and end of treatment.

  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) form 0 to 10 (0=lowest intensity and 10= highest intensity).

  5 weeks

Secondary Outcomes (12)

• Variation of averaged weekly frequency (number of episodes) of craving episodes between start and end of treatment.

  5 weeks

• Variation of averaged weekly duration (cumulative duration of all episodes) of craving episodes between start and end of treatment.

  5 weeks

• Variation of averaged weekly intensity, frequency and duration of craving episodes between start of treatment and 4 weeks after the end of treatment.

  9 weeks (5 weeks of treatment +4 weeks of follow up after treatment)

• Variation of averaged weekly frequency 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.

  9 weeks

• Variation of averaged weekly duration 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.

  9 weeks

Study Arms (2)

Nalmefene

EXPERIMENTAL

Drug: Nalmefene

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Nalmefene DRUG

Week 1: 18 mg/d Week 2: 1. In the absence of ARs or in the presence of grade 1 or 2 ARs, 36 mg/d 2. In the presence of grade 3 ARs, 18 mg/d 3. In the presence of grade 4 ARs, treatment will be stopped immediately. Week 3 to week 5: 1. In case of acceptable safety profile at the 18mg/d dosage during week 2, the treatment will be maintained at the same dosage 2. In the presence of sustained grade 3 ARs at the 18mg/d dosage during week 2, the treatment will be stopped. 3. In case of acceptable safety profile at the 36mg/d dosage during week 2, the treatment will be maintained at the same dosage 4. In the presence of grade 3 ARs at the 36mg/d dosage during week 2, the treatment dosage will be decreased at 18mg/d 5. Whatever the dosage during week 2, in the presence of grade 4 ARs, the treatment will be stopped immediately.

Nalmefene

Placebo DRUG

Week 1: 1 tablet/d Week 2: 1. In the absence of ARs or in the presence of grade 1 or 2 ARs, 2 tablets/d 2. In the presence of grade 3 ARs, 1 tablet/d 3. In the presence of grade 4 ARs, the treatment will be stopped immediately. Week 3 to week 5: 1. In case of acceptable safety profile at the dosage of 1 tablet/d during week 2, the treatment will be maintained at the same dosage 2. In the presence of sustained grade 3 ARs at the dosage of 1 tablet/d during week 2, the treatment will be stopped. 3. In case of acceptable safety profile at the dosage of 2 tablets/d during week 2, the treatment will be maintained at the same dosage 4. In the presence of grade 3 ARs at the dosage of 2 tablets/d during week 2, the treatment dosage will be decreased at 1 tablet/d 5. Whatever the dosage during week 2, in the presence of grade 4 ARs, the treatment will be stopped immediately.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females ≥ 18 years old
• Patient already in care or newly initiating care in Addictology departments for a beharioural addiction, diagnosed with current:
• Gambling disorder \[NORC DSM Screen for Gambling Problems (NODS), revised for DSM-5\]
• Food addiction \[Yale Food Addiction Scale (YFAS), revised for DSM-5\]
• Or Sexual addiction \[interview adapted from the NODS to explore the diagnostic criteria proposed by Carnes et al. (2012): NODS-SA\]
• Able to regularly assess and report their craving episodes on a weekly diary
• Who provide their written informed consent
• Affiliated with French social security system or beneficiary from such system
• use adequate contraceptive measures as recommended by the CTFG (Recommendations related to contraception and pregnancy testing in clinical trials v1.1), and have a negative pregnancy test (urine 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 (LH) and follicle stimulating hormone (FSH) levels corresponding to post-menopausal levels
• or have undergone irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy (this operation must be documented).

You may not qualify if:

• 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.);
• 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).
• Predictable opioid treatment during the study period;
• 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;
• 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);
• Extreme leanness (body mass index \< 16.5) (because loss of appetite and/or weight loss are frequent adverse effects of nalmefene);
• Current treatment with potent inhibitor drugs of the UGT2B7 (UDP-Glucuronosyltransferase-2B7); for example: diclofenac, fluconazole, medroxyprogesterone acetate, meclofenamic acid;

Sponsors & Collaborators

• Nantes University Hospital: lead

Study Sites (13)

CHU de Besançon

Besançon, France

NOT YET RECRUITING

CHU de Bordeaux

Bordeaux, 33000, France

RECRUITING

CHRU de Brest

Brest, 29200, France

RECRUITING

CHU de Clermont Ferrand

Clermont-Ferrand, 63000, France

RECRUITING

CHU de Dijon

Dijon, 21000, France

NOT YET RECRUITING

CH de La Rochelle

La Rochelle, 17000, France

RECRUITING

Hospices Civils de Lyon

Lyon, 69000, France

RECRUITING

CHU de Montpellier

Montpellier, 34295, France

NOT YET RECRUITING

CHU de Nantes

Nantes, France

RECRUITING

CHU de Nîmes

Nîmes, 30000, France

RECRUITING

Hôpitaux Universitaires de Strasbourg

Strasbourg, 67000, France

RECRUITING

CHRU de Tours

Tours, 37000, France

RECRUITING

Hôpital Paul Brousse

Villejuif, 94800, France

RECRUITING

MeSH Terms

Conditions

Gambling; Food Addiction; Compulsive Sexual Behavior Disorder

Interventions

nalmefene

Condition Hierarchy (Ancestors)

Risk-Taking; Behavior; Disruptive, Impulse Control, and Conduct Disorders; Mental Disorders; Behavior, Addictive; Compulsive Behavior; Impulsive Behavior; Feeding and Eating Disorders; Sexual and Gender Disorders; Sexual Dysfunctions, Psychological

Study Officials

• Marie GRALL-BRONNEC

  Nantes University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marie GRALL-BRONNEC

CONTACT

+33240847620; marie.bronnec@chu-nantes.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2022
• First Posted: September 14, 2022
• Study Start: March 31, 2023
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: February 12, 2025

Record last verified: 2025-02

Locations

FR (13)