Oxytocin and Naltrexone: Investigation of Combined Effects on Stress- and Alcohol Cue-induced Craving in Alcohol Use Disorder

NCT ID: NCT05093296

Last Updated: 2024-03-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 62 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-02
• Study Completion Date: 2023-09-27

Brief Summary

Alcohol use disorder (AUD) is a chronic relapsing disorder. Alcohol craving, a hallmark symptom of AUD that drives relapse in patients, is only insufficiently treated by existing medication. One promising new compound is Oxytocin (OXY), which showed beneficial effects on alcohol craving in preliminary clinical studies. Additionally, OXY seems to enhance effects of established medication, specifically Naltrexone (NTX), an opioid-antagonist which is approved for AUD treatment via positive synergism on neurotransmitter levels. The proposed two-armed, 1:1 randomized, double-blind, parallel group trial seeks to test the putative synergistic effects of combined intranasal OXY spray (24 IU) + oral NTX (50mg) against Placebo spray + oral NTX (50mg) on alcohol craving (primary outcome) in male and female patients with AUD that suffer from high alcohol craving, within the framework of a validated alcohol cue-and stress-exposure task (i.e. a combined Trier Stress Test and alcohol cue-exposure) that was established for screening new medications in AUD and determine their effects on craving and relapse risk. Treatment effects on additional neurobiological and biochemical markers of craving that show strong associations to individual relapse risk, will serve as secondary outcomes. Collection and analysis of follow-up data (90 days) will be performed to determine whether treatment effects relate to patient outcome.

The clinical trial period for an individual participant consists of a screening visit (visit 1), a baseline visit (visit 2) and two treatment visits (visits 3 and 4)(all within equal or less than ten days) followed by a 90 days (+/- 7 days) follow-up phase with two visits (visits 5 and 6) at day 30 (± 7 days) and day 90 (± 7 days). Visits 1 to 4 will be conducted while participants are undergoing standard in-patient treatment at the Department of Addictive Behavior and Addiction medicine at the Central Institute of Mental Health (CIMH) in Mannheim, Germany, for the medical condition under investigation.

Conditions

Alcohol Use Disorder; Alcoholism; Alcohol Addiction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Oxytocin + Naltrexone

All patients will receive 50mg Naltrexone daily (NTX, oral tablet) in the course of standard in-patient treatment. In the experimental group, patients will receive a single dose of 24 I.U. oxytocin nasal spray at two study visits during in-patient treatment:

• Visit 2 - First Application of Oxytocin 40 minutes prior to a combined stress- and alcohol cue-exposure during visit 2
• Visit 3 - Second Application of Oxytocin 40 minutes prior to an fMRI-based assessment of alcohol cue-reactivity

Group Type: EXPERIMENTAL

Oxytocin nasal spray

Intervention Type: DRUG

24 I.U. Oxytocin nasal Spray will be administered twice on two separate trial days.

Naltrexone Pill

Intervention Type: DRUG

All participants will receive 50mg Naltrexone daily as oral tablet throughout the study

Placebo + Naltrexone

All patients will receive 50mg Naltrexone daily (NTX, oral tablet) in the course of standard in-patient treatment. In the comparator group, patients will receive a placebo nasal spray (same composition as the verum oxytocin spray except for the active ingredient oxytocin) at two study visits during in-patient treatment:

• Visit 2 - First Application of Placebo 40 minutes prior to a combined stress- and alcohol cue-exposure during visit 2
• Visit 3 - Second Application of Placebo 40 minutes prior to an fMRI-based assessment of alcohol cue-reactivity

Group Type: ACTIVE_COMPARATOR

Naltrexone Pill

Intervention Type: DRUG

All participants will receive 50mg Naltrexone daily as oral tablet throughout the study

Placebo

Intervention Type: DRUG

Placebo nasal spray (same composition as the verum oxytocin spray except for the active ingredient oxytocin)

Interventions

Oxytocin nasal spray

24 I.U. Oxytocin nasal Spray will be administered twice on two separate trial days.

Intervention Type: DRUG

Naltrexone Pill

All participants will receive 50mg Naltrexone daily as oral tablet throughout the study

Intervention Type: DRUG

Placebo

Placebo nasal spray (same composition as the verum oxytocin spray except for the active ingredient oxytocin)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age between 18 and 70 years
• Patients meeting the diagnosis of an alcohol dependence according to the Internation Clasification of Diseases 10th revision (ICD10)
• Patients with at least moderate craving, i.e. either >=15 points on the Alcohol Urge Questionnaire (AUQ, range 8 to 56 points) craving scale or increase in AUQ scores by >= 50% after exposure to visual alcohol cues (i.e. minimum increase of >=4 points after cue exposure)
• Ability of the individual to understand the character and the individual consequences of the clinical trial
• Written informed consent (must be available before enrollment in the study)
• Consent to random assignment
• For women with childbearing potential, use of a highly effective birth control method until 24 hours after Visit 4 and negative pregnancy test

Exclusion Criteria

• Subjects presenting with any of the following criteria will not be included in the clinical trial: Current psychotic or bipolar disorder or current severe depressive episode with suicidal ideations
• Current treatment with any of the following substances: Any investigational medicinal product, Opioid-containing Analgesics, Anorexics, Anticonvulsants, Opioid-containing Antidiarrheal Agents, Antineoplastics, Antipsychotics (exception: episodic use of melperone, pipamperone and quetiapine are allowed), Antidepressants (exception: allowed, when being taken in stable dose for a minimum of 14 days prior to enrolment and/or doxepin in low doses [max. 75mg daily]), Opioid-containing Cough/cold agents, systemic Steroids
• Positive drug screening (amphetamines/ecstasy, opiates, cocaine, barbiturates)
• Pregnancy, lactation or breastfeeding
• Current severe somatic comorbidities: liver cirrhosis [CHILD B or C] or impaired renal function [glomerular filtration rate (GFR)<15ml/Min] [each determined by physical examination and/or laboratory testing], severe heart insufficiency [determined by assessment of medical history], pre-existing epilepsy [determined by assessment of medical history], long-QT syndrome or cardial arrhythmia [determined by ECG]
• History of hypersensitivity to the investigational medicinal product Oxytocin (Syntocinon®) and/or Naltrexone (trade names: Adepend, Naltrexon-Hcl neuraxpharm, Naltrexonhydrochlorid Accord) or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product Oxytocin (Syntocinon®) and/or Naltrexone
• Participation in other clinical trials or observation period of competing clinical trials, respectively.
• Acute suicidal tendency or acute endangerment of self and others

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Heidelberg University - Institute of Medical Biometry (IMBI)

UNKNOWN

Sponsor Role: collaborator

Heidelberg University - Coordination Centre for Clinical Trials (KKS) of Heidelberg University

UNKNOWN

Sponsor Role: collaborator

German Federal Ministry of Education and Research

OTHER_GOV

Sponsor Role: collaborator

Central Institute of Mental Health, Mannheim

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Patrick Bach, MD

Role: STUDY_DIRECTOR

Central Institute of Mental Health, Mannheim

Locations

Central Institute of Mental Health

Mannheim, , Germany

Countries

Germany

References

Zimmermann S, Thomas BC, Krisam J, Limprecht R, Klose C, Stenger M, Pourbaix M, Ries M, Vollstaedt-Klein S, Koopmann A, Lenz B, Kiefer F, Bach P. ON-ICE trial: Investigation of the combined effects of oxytocin and naltrexone on stress-induced and alcohol cue-induced craving in alcohol use disorder-Study protocol of a phase II randomised double-blind placebo-controlled parallel-group trial. BMJ Open. 2022 Apr 11;12(4):e059672. doi: 10.1136/bmjopen-2021-059672.

Reference Type: DERIVED

PMID: 35410938 (View on PubMed)

Other Identifiers

CIMH ON-ICE 21

Identifier Type: -

Identifier Source: org_study_id