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

NCT05093296 | Completed Phase 2 DMC

• 1 other identifier: CIMH ON-ICE 21
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Alcohol Urge Questionnaire (AUQ)

  Subjective Alcohol Craving will be assessed at separate time points before and after Oxytocin Administration using the AUQ

  60 minutes after oxytocin/placebo application and directly after the combined stress- and cue-exposure will serve as primary outcome measure at Visit 3

Secondary Outcomes (24)

• Alcohol Urge Questionnaire (AUQ)

  35 minutes after oxytocin/placebo application at Visit 3

• Alcohol Urge Questionnaire (AUQ)

  70 minutes after oxytocin/placebo application at Visit 3

• Alcohol Urge Questionnaire (AUQ)

  80 minutes after oxytocin/placebo application at Visit 3

• Alcohol Urge Questionnaire (AUQ)

  90 minutes after oxytocin/placebo application at Visit 3

• Alcohol Urge Questionnaire (AUQ)

  85 minutes after oxytocin/placebo application, i.e. directly fMRI session at Visit 4

Study Arms (2)

Oxytocin + Naltrexone

EXPERIMENTAL

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

Drug: Oxytocin nasal spray; Drug: Naltrexone Pill

Placebo + Naltrexone

ACTIVE COMPARATOR

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

Drug: Naltrexone Pill; Drug: Placebo

Interventions

Oxytocin nasal spray DRUG

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

Oxytocin + Naltrexone

Naltrexone Pill DRUG

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

Oxytocin + Naltrexone; Placebo + Naltrexone

Placebo DRUG

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

Placebo + Naltrexone

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Central Institute of Mental Health, Mannheim: lead
• Heidelberg University - Institute of Medical Biometry (IMBI): collaborator
• Heidelberg University - Coordination Centre for Clinical Trials (KKS) of Heidelberg University: collaborator
• German Federal Ministry of Education and Research: collaborator

Study Sites (1)

Central Institute of Mental Health

Mannheim, 68159, Germany

Location

Related Publications (1)

• 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.

  PMID: 35410938 DERIVED

MeSH Terms

Conditions

Alcoholism

Interventions

Naltrexone

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Patrick Bach, MD

  Central Institute of Mental Health, Mannheim

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• 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: October 13, 2021
• First Posted: October 26, 2021
• Study Start: December 2, 2021
• Primary Completion: July 15, 2023
• Study Completion: September 27, 2023
• Last Updated: March 29, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data will be available upon publication of the results until 3 years after that.
• Access Criteria: Individual data will be shared with researchers who provide a methodologically sound proposal (sent to the Principal Investigator/Study Chair of the Trial).

Locations

DE (1)