Intranasal Insulin for Alcoholism

(ITA Trial)

Overseen By Carolina L Haass-Koffler

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Brown University

Must not be taking: Stimulants, Opioids, others

Disqualifiers: Diabetes, Pregnancy, Substance use disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 day

40 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you do not use medications that may interact with insulin and alcohol. It's best to discuss your current medications with the trial team to see if they are allowed.

What data supports the effectiveness of the drug intranasal insulin for treating alcoholism?

Research shows that intranasal insulin, particularly insulin detemir, has been effective in improving memory in people with mild cognitive impairment or early Alzheimer's disease. This suggests that intranasal insulin might have beneficial effects on brain function, which could potentially help in treating alcoholism. ^{1 2 3 4 5}

Is intranasal insulin safe for humans?

Intranasal insulin has been studied in healthy volunteers and people with diabetes, showing a safety profile that is generally well-tolerated. Studies have also explored its use in people with mild cognitive impairment or Alzheimer's disease, indicating it is safe for short-term use. ^{2 4 5 6 7}

How does the drug intranasal insulin differ from other treatments for alcoholism?

Intranasal insulin is unique because it is administered through the nose, which allows it to act quickly and directly on the brain, potentially reducing cravings and stress responses associated with alcoholism. This method is different from traditional treatments that often involve oral medications or counseling. ^{1 2 3 8 9}

What is the purpose of this trial?

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.

Eligibility Criteria

This trial is for adults over 21 with Alcohol Use Disorder who regularly consume alcohol and are in good health. Participants must understand English at an 8th grade level, agree to glucose monitoring by finger stick, and meet DSM-5 criteria for AUD. They cannot participate if they don't adhere to study procedures.

Inclusion Criteria

Good health as confirmed by medical history, physical examination and lab tests

Understand informed consent and questionnaires in English at an 8th grade level

I am willing to have my glucose levels checked by finger stick.

Exclusion Criteria

History of suicide attempts in the last three years

I am not pregnant or breastfeeding.

Hypersensitivity to insulin

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single dose of intranasal insulin or placebo followed by an alcohol challenge

1 day

1 visit (in-person)

Washout

A one-week washout period between crossover treatments

1 week

Crossover Treatment

Participants receive the alternate treatment (insulin or placebo) followed by an alcohol challenge

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

Treatment Details

Interventions

• Intranasal Insulin

Trial Overview The trial tests the effects of intranasal insulin versus a saline placebo on individuals with Alcohol Use Disorder in a controlled bar setting. Each participant will try both treatments at different times (crossover design) without knowing which one they're getting (double-blind).

Participant Groups

Group I: Placebo, Then Insulin Experimental Treatment 1 Intervention

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.

Group II: Insulin, Then Placebo Experimental Treatment 1 Intervention

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.

Intranasal Insulin is already approved in United States, European Union for the following indications:

Approved in United States as Intranasal insulin for:

• Diabetes

Approved in European Union as Intranasal insulin for:

• Diabetes

Who Is Running the Clinical Trial?

Brown University

Lead Sponsor

Trials

480

Recruited

724,000+

Findings from Research

In a study involving 16 type 1 diabetic patients, gelified nasal insulin was found to be as effective as subcutaneous regular insulin in managing blood sugar levels, with comparable HbA1c results after six months.

While nasal insulin showed better tolerance compared to a previously tested form, some patients experienced nasal discomfort, indicating a need for further research to enhance nasal tolerance and improve insulin absorption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Six month administration of gelified intranasal insulin in 16 type 1 diabetic patients under multiple injections: efficacy vs subcutaneous injections and local tolerance. Lalej-Bennis, D., Boillot, J., Bardin, C., et al.[2022]

In a trial involving 60 adults with mild cognitive impairment (MCI) or Alzheimer's disease (AD), intranasal insulin detemir at a dose of 40 IU showed significant improvements in memory and working memory compared to placebo, particularly benefiting APOE-ε4 carriers.

The study found that higher baseline insulin resistance predicted greater cognitive improvement with the 40 IU dose, but no significant effects were observed on daily functioning or executive functioning, indicating a specific impact on cognitive aspects rather than overall daily activities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-acting intranasal insulin detemir improves cognition for adults with mild cognitive impairment or early-stage Alzheimer's disease dementia. Claxton, A., Baker, LD., Hanson, A., et al.[2022]

The study demonstrated that administering intranasal insulin in a single nostril significantly enhances absorption, achieving higher maximum concentrations (C(max)) compared to dual nostril administration, with maximum levels reaching 96 µU/ml for a 75 U dose.

The enhanced absorption was attributed to the increased amount of insulin administered rather than the absorption enhancer CPE-215, indicating that higher doses of insulin can improve its effectiveness when delivered intranasally.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced absorption of Nasulin™, an ultrarapid-acting intranasal insulin formulation, using single nostril administration in normal subjects. Stote, R., Miller, M., Marbury, T., et al.[2021]

The intranasal insulin formulation (Nasulin) was well tolerated in a study of 13 healthy male volunteers, showing a significant rise in serum insulin and a decrease in plasma glucose after administration.

Nasulin demonstrated a peak insulin absorption time of 10-20 minutes, with a relative absorption of 12.0% from the dominant nostril and 15.4% from the nondominant nostril, indicating it can be effectively administered regardless of nasal cycle.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics of intranasal insulin spray (Nasulin) administered to healthy male volunteers: infuence of the nasal cycle. Leary, AC., Dowling, M., Cussen, K., et al.[2021]

Intranasal insulin (INI) was found to be safe for older adults with diabetes who were already using systemic insulins, showing no serious adverse events, hypoglycemic episodes, or weight gain during the 24-week trial.

The study indicated that INI treatment led to a decrease in glycemic variability and a long-term trend towards lower HbA1c and plasma glucose levels, suggesting potential benefits for managing diabetes, although further research is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Intranasal Insulin in Type 2 Diabetes on Systemic Insulin: A Double-Blinded Placebo-Controlled Sub-Study of Memaid Trial. Aponte Becerra, L., Galindo Mendez, B., Khan, F., et al.[2022]

In a 32-week study involving 686 patients with Type 2 diabetes, insulin detemir (IDet) therapy was found to be safe, with no serious adverse drug reactions reported and a significant reduction in total hypoglycemic events from 435 to 204.

Patients experienced improved glycemic control, as indicated by a decrease in glycated hemoglobin A1c from 9.9% to 7.7% and fasting plasma glucose from 11.9 mmol/L to 7.4 mmol/L, alongside a slight reduction in body weight.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical safety of insulin detemir in patients with Type 2 diabetes in the Gulf countries: The multicenter, noninterventional, open-label LevSafe study. El Shiekh, AR., Farrag, HA., Ashour, T., et al.[2020]

In a study involving 1540 patients with type 2 diabetes from the ASEAN region, insulin detemir (IDet) was found to be safe and effective, significantly improving glucose control over 24 weeks without increasing the risk of major hypoglycaemia.

The overall incidence of hypoglycaemia decreased dramatically from 1.73 to 0.46 events per patient-year, and patients also experienced improvements in their lipid profiles and blood pressure, while maintaining stable body weight.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of insulin detemir in type 2 diabetes: results from the ASEAN cohort of the A₁chieve study. Soewondo, P., Mohamed, M., Jain, AB., et al.[2022]

Intranasal insulin delivery mimics the natural 'pulsatile' release of insulin during meals and has a pharmacokinetic profile similar to intravenous insulin, making it a promising alternative to subcutaneous injections for diabetes management.

Effective absorption of insulin through the nasal route requires the use of absorption enhancers to improve permeability and prolong the drug's residence time in the nasal cavity, addressing the barriers that limit its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intranasal insulin delivery and therapy. Hinchcliffe, M., Illum, L.[2019]

Intranasal insulin significantly reduced nicotine cravings in smokers during acute abstinence, with effects observed in both a crossover trial of 19 participants and a parallel study of 37 participants, indicating its potential as a smoking cessation aid.

The treatment was found to be safe, as it did not cause changes in peripheral insulin levels, suggesting that its effects on cravings and stress responses are centrally mediated in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduction of smoking urges with intranasal insulin: a randomized, crossover, placebo-controlled clinical trial. Hamidovic, A., Khafaja, M., Brandon, V., et al.[2018]

References

1. France pubmed.ncbi.nlm.nih.gov

Six month administration of gelified intranasal insulin in 16 type 1 diabetic patients under multiple injections: efficacy vs subcutaneous injections and local tolerance. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Long-acting intranasal insulin detemir improves cognition for adults with mild cognitive impairment or early-stage Alzheimer's disease dementia. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Enhanced absorption of Nasulin™, an ultrarapid-acting intranasal insulin formulation, using single nostril administration in normal subjects. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics of intranasal insulin spray (Nasulin) administered to healthy male volunteers: infuence of the nasal cycle. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Safety of Intranasal Insulin in Type 2 Diabetes on Systemic Insulin: A Double-Blinded Placebo-Controlled Sub-Study of Memaid Trial. [2022]

6. India pubmed.ncbi.nlm.nih.gov

Clinical safety of insulin detemir in patients with Type 2 diabetes in the Gulf countries: The multicenter, noninterventional, open-label LevSafe study. [2020]

7. Ireland pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of insulin detemir in type 2 diabetes: results from the ASEAN cohort of the A₁chieve study. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Intranasal insulin delivery and therapy. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Reduction of smoking urges with intranasal insulin: a randomized, crossover, placebo-controlled clinical trial. [2018]