Intranasal Insulin for Treatment of Alcohol Use Disorder (ITA)

This is a randomized controlled trial (RCT), within-subject, crossover, double-blind, placebo-controlled in non-treatment-seeking individuals with Alcohol Use Disorder (AUD) (N=40, 50% female) randomized to IN insulin or placebo. In a bar laboratory setting, randomized participants will receive a single dose of IN insulin (80IU) or an IN matched placebo (0.9% Saline). Participants will undergo a cue-reactivity paradigm followed by an alcohol challenge that includes an alcohol drink designed to raise the breath alcohol content (BrAC) to 0.08g/dL.

Study Overview

• Status: Recruiting
• Conditions: Alcohol Use Disorder
• Intervention / Treatment: Drug: Regular Human Insulin then Placebo; Drug: Placebo then Regular Human Insulin

Detailed Description

Aims in this RCT testing the effect of IN insulin, compared to placebo, in individuals with AUD include the following:

AIM 1: to assess the safety, tolerability and acceptability of IN insulin as a pharmacological intervention for AUD. The data collected in this aim will monitor possible adverse events and yield qualitative and quantitative data to finalize the feasibility and acceptability of IN insulin as an AUD pharmacotherapy.

Aim 2 (alcohol-drug interaction): to assess the safety and tolerability of IN insulin when administered with alcohol. The investigators will use a battery of physiological/psychological assessments that measures potential adverse events, alcohol subjective response and alcohol pharmacokinetics endpoints.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Carolina L Haass-Koffler; Phone Number: 4155191385; Email: carolina_haass-koffler@brown.edu

Study Locations

• United States
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Recruiting
      • Brown University
      • Contact: Brian Gully; Phone Number: (401) 863-6646; Email: alcohol-stress-study@brown.edu
      • Contact: Zoe Brown; Phone Number: (401) 863-6646; Email: alcohol-stress-study@brown.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ≥21 years

  • meet any DSM-5 criteria score for AUD
  • Individuals who, in the last month, have consumed at least the same amount of alcohol that will be administered in the laboratory procedure (i.e. to reach BrAC levels of 0.08g/dl, ~two drinks in one occasion)
  • BrAC=0.00g/dL at each visit
  • good health as confirmed by medical history, physical examination and lab tests
  • willing to adhere to the study procedures
  • understand informed consent and questionnaires in English at an 8th grade level
  • willing to have glucose monitored by finger stick during the laboratory procedures

Exclusion Criteria:

• • female identifying who are breastfeeding or pregnant (assessed by a urine screen)

  • individuals with diabetes
  • history of suicide attempts in the last three years
  • current diagnosis of other substance use disorder (other than nicotine or cannabis)
  • use of drugs (e.g. stimulants/opioids) at each alcohol administration session (by urine tox screen)
  • cannabis intoxication (by clinical assessments)
  • use of medications that may interact with insulin and alcohol (by Micromedex database)
  • hypersensitivity to insulin
  • any nasal disease/congestion that may interfere with intranasal drug absorption;
  • baseline hypoglycemia (blood glucose ≤65mg/dL) or hyperglycemia (blood glucose >200mg/dL) (by finger stick)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Insulin, Then Placebo; There will be one single administration of intranasal human insulin (80IU) before alcohol self-administration. After a one week washout period, there will be one single intranasal administration of placebo (saline, 0.9% solution) before alcohol self administration.	Drug: Regular Human Insulin then Placebo; Insulin: 80 IU (administered intranasally) THEN Placebo: 0.9% saline solution (administered intranasally); Other Names: Novolin R
Experimental: Placebo, Then Insulin; There will be one single intranasal administration of placebo (saline, 0.9% solution) before alcohol self administration. After a one week washout period, there will be one single administration of intranasal human insulin (80IU) before alcohol self-administration.	Drug: Placebo then Regular Human Insulin; Placebo: 0.9% saline solution (administered intranasally) THEN Insulin: 80 IU (administered intranasally); Other Names: Novolin R

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
intranasal adverse events	Adverse event reported during the drug administration	From baseline to post-treatment (1 day)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
insulin alcohol interaction	Adverse event reported during the alcohol administration	From baseline to post-treatment (1 day)

Collaborators and Investigators

• Sponsor: Brown University

Publications and helpful links

General Publications

• Haass-Koffler CL, Kashyap B, Gully BJ, Nambiar SS, Hornbacher R, Foster SL, Silberman Y, Swift RM, Hanson LR, Frey WH 2nd. Intranasal insulin for the treatment of alcohol use disorder: design and methodology of an alcohol interaction randomized controlled trial. Contemp Clin Trials Commun. 2025 Jun 10;46:101509. doi: 10.1016/j.conctc.2025.101509. eCollection 2025 Aug.

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): January 31, 2027

Study Registration Dates

• First Submitted: July 25, 2023
• First Submitted That Met QC Criteria: August 9, 2023
• First Posted (Actual): August 14, 2023

Study Record Updates

• Last Update Posted (Estimated): September 5, 2025
• Last Update Submitted That Met QC Criteria: August 28, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Alcoholism; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptide Hormones; Peptides; Amino Acids, Peptides, and Proteins; Pancreatic Hormones; Insulins
• Other Study ID Numbers: STUDY00000134

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No