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

November 7, 2023 updated by: Nantes University Hospital

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

266

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • France
      • Besançon, France
        • Not yet recruiting
        • CHU de Besancon
        • Contact:
        • Principal Investigator:
          • Julie GIUSTINIANI, Dr
      • Bordeaux, France, 33000
      • Brest, France, 29200
        • Recruiting
        • CHRU de Brest
        • Contact:
        • Principal Investigator:
          • Morgane GUILLOU-LANDREAT
      • Clermont-Ferrand, France, 63000
      • La Rochelle, France, 17000
      • Lyon, France, 69000
      • Nantes, France
      • Nîmes, France, 30000
      • Strasbourg, France, 67000
      • Tours, France, 37000
      • Villejuif, France, 94800
        • Recruiting
        • Hopital Paul Brousse
        • Contact:
        • Principal Investigator:
          • Amine Benyamina

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Pre-inclusion Criteria:

  • 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

Inclusion Criteria:

  • Having presented at least one episode of craving with an intensity ≥ 4/10 at the NRS during the week prior to inclusion

Women must meet one of the following criteria at the time of inclusion:

  • 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).

Exclusion Criteria:

  • 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;
  • Current treatment with UGT inducing drugs; for example: dexamethasone, phenobarbital, rifampicin, omeprazole;
  • 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);
  • Pregnancy (attested by a pregnancy urinary test for women of childbearing age) or breastfeeding woman;
  • Trusteeship;
  • Major cognitive impairment;
  • Not fluent in French;
  • Participation to another interventional study during the last month or expected participation to another interventional study during participation to the NABAB study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Drug: Placebo

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.
Experimental: Nalmefene
Drug: Nalmefene

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Variation of averaged intensity of craving episodes between start and end of treatment.
Time Frame: 5 weeks
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Variation of averaged weekly frequency (number of episodes) of craving episodes between start and end of treatment.
Time Frame: 5 weeks
5 weeks
Variation of averaged weekly duration (cumulative duration of all episodes) of craving episodes between start and end of treatment.
Time Frame: 5 weeks
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.
Time Frame: 9 weeks (5 weeks of treatment +4 weeks of follow up after 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.
Time Frame: 9 weeks
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.
Time Frame: 9 weeks
9 weeks
Variation of averaged weekly intensity 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.
Time Frame: 9 weeks
Assessed through a Numerical Rating Scale (NRS) form 0 (lowest intensity) to 10 (highest intensity)
9 weeks
Overall clinical improvement, assessed though the Clinical Global Impression - Improvement (CGI-I) scale.
Time Frame: 9 weeks
9 weeks
Overall clinical improvement, assessed though the GGI - Efficacy Index (CGI-EI).
Time Frame: 9 weeks
9 weeks
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
Time Frame: 9 weeks
9 weeks
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.
Time Frame: 9 weeks
9 weeks
Mutation(s) associated with non-response to nalmefene treatment
Time Frame: 9 weeks
9 weeks
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
Time Frame: 1 week
1 week

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nantes University Hospital

Investigators

  • Principal Investigator: Marie GRALL-BRONNEC, Nantes University Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 31, 2023

Primary Completion (Estimated)

July 1, 2025

Study Completion (Estimated)

July 1, 2025

Study Registration Dates

First Submitted

September 6, 2022

First Submitted That Met QC Criteria

September 9, 2022

First Posted (Actual)

September 14, 2022

Study Record Updates

Last Update Posted (Estimated)

November 9, 2023

Last Update Submitted That Met QC Criteria

November 7, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RC21_0336

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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