Intranasal insulin for the treatment of alcohol use disorder: design and methodology of an alcohol interaction randomized controlled trial
Despite developments in treatments for alcohol use disorder (AUD), current pharmacotherapies face several limitations, including adverse events. Intranasal (IN) insulin has shown promise for addictive disorders. The overarching hypothesis of this trial is that by increasing brain cell energy and glu...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-08-01
|
| Series: | Contemporary Clinical Trials Communications |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2451865425000833 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850073864663465984 |
|---|---|
| author | Carolina L. Haass-Koffler Bhavani Kashyap Brian J. Gully Sithara S. Nambiar Rivkah Hornbacher Stephanie L. Foster Yuval Silberman Robert M. Swift Leah R. Hanson William H. Frey, II |
| author_facet | Carolina L. Haass-Koffler Bhavani Kashyap Brian J. Gully Sithara S. Nambiar Rivkah Hornbacher Stephanie L. Foster Yuval Silberman Robert M. Swift Leah R. Hanson William H. Frey, II |
| author_sort | Carolina L. Haass-Koffler |
| collection | DOAJ |
| description | Despite developments in treatments for alcohol use disorder (AUD), current pharmacotherapies face several limitations, including adverse events. Intranasal (IN) insulin has shown promise for addictive disorders. The overarching hypothesis of this trial is that by increasing brain cell energy and glucose metabolism, while reducing stress hormones, IN insulin may be an ideal approach for treating multiple domains of AUD including memory, executive function and impulsivity. Preclinical and clinical studies of IN insulin demonstrate that it is a safe and effective method for delivering insulin to the central nervous system, circumventing the blood brain barrier, and reducing adverse events associated with insulin use (hypoglycemia). The overarching goal of this Phase I/IIa, within-subject, crossover, double-blind, placebo-controlled, alcohol interaction trial is to test the IN insulin (80IU), compared to placebo (0.9 % saline) as a potential therapy for AUD. The primary aim assesses the safety and tolerability of IN insulin, compared to placebo, in individuals with AUD (N = 40) who are not currently seeking treatment. The secondary aim assesses the safety and tolerability of IN insulin, compared to placebo, when co-administered with alcohol (0.08 g/dL). Tertiary aims include assessing cognitive performance, memory, and impulsivity following IN insulin, or placebo, and alcohol administration. Finally, an alcohol cue reactivity procedure investigates the effect of IN insulin, compared to placebo, in alcohol craving. This is the first study to evaluate IN insulin in an AUD population and this manuscript describes the rationale, design, and methodology of the alcohol interaction trial. This study is designed to accelerate research for the development of novel medications to treat AUD and provide empirical evidence on the safety and efficacy of a neurotherapeutic approach to inform clinical practice. Clinical trial: NCT05988632. Fda/ind: 168417. |
| format | Article |
| id | doaj-art-57bbf11ad43640318c9334a8a98dcc36 |
| institution | DOAJ |
| issn | 2451-8654 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Contemporary Clinical Trials Communications |
| spelling | doaj-art-57bbf11ad43640318c9334a8a98dcc362025-08-20T02:46:43ZengElsevierContemporary Clinical Trials Communications2451-86542025-08-014610150910.1016/j.conctc.2025.101509Intranasal insulin for the treatment of alcohol use disorder: design and methodology of an alcohol interaction randomized controlled trialCarolina L. Haass-Koffler0Bhavani Kashyap1Brian J. Gully2Sithara S. Nambiar3Rivkah Hornbacher4Stephanie L. Foster5Yuval Silberman6Robert M. Swift7Leah R. Hanson8William H. Frey, II9Center for Alcohol and Addiction Studies, Brown University, Providence, RI, USA; Department of Psychiatry and Human Behavior, Warren Alpert Medical School, Brown University, Providence, RI, USA; Department of Behavioral and Social Sciences, School of Public Health, Brown University, Providence, RI, USA; Carney Institute for Brain Science, Providence RI, Brown University, RI, USA; Corresponding author. 121 South Main Street Providence, RI, 02903, USA.HealthPartners Institute, Bloomington, MN, USACenter for Alcohol and Addiction Studies, Brown University, Providence, RI, USACenter for Alcohol and Addiction Studies, Brown University, Providence, RI, USACenter for Alcohol and Addiction Studies, Brown University, Providence, RI, USA; Pennsylvania State College of Medicine, Hershey, PA, USADepartment of Psychiatry and Human Behavior, Warren Alpert Medical School, Brown University, Providence, RI, USAPennsylvania State College of Medicine, Hershey, PA, USACenter for Alcohol and Addiction Studies, Brown University, Providence, RI, USA; Department of Psychiatry and Human Behavior, Warren Alpert Medical School, Brown University, Providence, RI, USA; Department of Behavioral and Social Sciences, School of Public Health, Brown University, Providence, RI, USAHealthPartners Institute, Bloomington, MN, USAHealthPartners Institute, Bloomington, MN, USADespite developments in treatments for alcohol use disorder (AUD), current pharmacotherapies face several limitations, including adverse events. Intranasal (IN) insulin has shown promise for addictive disorders. The overarching hypothesis of this trial is that by increasing brain cell energy and glucose metabolism, while reducing stress hormones, IN insulin may be an ideal approach for treating multiple domains of AUD including memory, executive function and impulsivity. Preclinical and clinical studies of IN insulin demonstrate that it is a safe and effective method for delivering insulin to the central nervous system, circumventing the blood brain barrier, and reducing adverse events associated with insulin use (hypoglycemia). The overarching goal of this Phase I/IIa, within-subject, crossover, double-blind, placebo-controlled, alcohol interaction trial is to test the IN insulin (80IU), compared to placebo (0.9 % saline) as a potential therapy for AUD. The primary aim assesses the safety and tolerability of IN insulin, compared to placebo, in individuals with AUD (N = 40) who are not currently seeking treatment. The secondary aim assesses the safety and tolerability of IN insulin, compared to placebo, when co-administered with alcohol (0.08 g/dL). Tertiary aims include assessing cognitive performance, memory, and impulsivity following IN insulin, or placebo, and alcohol administration. Finally, an alcohol cue reactivity procedure investigates the effect of IN insulin, compared to placebo, in alcohol craving. This is the first study to evaluate IN insulin in an AUD population and this manuscript describes the rationale, design, and methodology of the alcohol interaction trial. This study is designed to accelerate research for the development of novel medications to treat AUD and provide empirical evidence on the safety and efficacy of a neurotherapeutic approach to inform clinical practice. Clinical trial: NCT05988632. Fda/ind: 168417.http://www.sciencedirect.com/science/article/pii/S2451865425000833Alcohol use disorder (AUD)InsulinNeurotherapeuticsIntranasal administration |
| spellingShingle | Carolina L. Haass-Koffler Bhavani Kashyap Brian J. Gully Sithara S. Nambiar Rivkah Hornbacher Stephanie L. Foster Yuval Silberman Robert M. Swift Leah R. Hanson William H. Frey, II Intranasal insulin for the treatment of alcohol use disorder: design and methodology of an alcohol interaction randomized controlled trial Contemporary Clinical Trials Communications Alcohol use disorder (AUD) Insulin Neurotherapeutics Intranasal administration |
| title | Intranasal insulin for the treatment of alcohol use disorder: design and methodology of an alcohol interaction randomized controlled trial |
| title_full | Intranasal insulin for the treatment of alcohol use disorder: design and methodology of an alcohol interaction randomized controlled trial |
| title_fullStr | Intranasal insulin for the treatment of alcohol use disorder: design and methodology of an alcohol interaction randomized controlled trial |
| title_full_unstemmed | Intranasal insulin for the treatment of alcohol use disorder: design and methodology of an alcohol interaction randomized controlled trial |
| title_short | Intranasal insulin for the treatment of alcohol use disorder: design and methodology of an alcohol interaction randomized controlled trial |
| title_sort | intranasal insulin for the treatment of alcohol use disorder design and methodology of an alcohol interaction randomized controlled trial |
| topic | Alcohol use disorder (AUD) Insulin Neurotherapeutics Intranasal administration |
| url | http://www.sciencedirect.com/science/article/pii/S2451865425000833 |
| work_keys_str_mv | AT carolinalhaasskoffler intranasalinsulinforthetreatmentofalcoholusedisorderdesignandmethodologyofanalcoholinteractionrandomizedcontrolledtrial AT bhavanikashyap intranasalinsulinforthetreatmentofalcoholusedisorderdesignandmethodologyofanalcoholinteractionrandomizedcontrolledtrial AT brianjgully intranasalinsulinforthetreatmentofalcoholusedisorderdesignandmethodologyofanalcoholinteractionrandomizedcontrolledtrial AT sitharasnambiar intranasalinsulinforthetreatmentofalcoholusedisorderdesignandmethodologyofanalcoholinteractionrandomizedcontrolledtrial AT rivkahhornbacher intranasalinsulinforthetreatmentofalcoholusedisorderdesignandmethodologyofanalcoholinteractionrandomizedcontrolledtrial AT stephanielfoster intranasalinsulinforthetreatmentofalcoholusedisorderdesignandmethodologyofanalcoholinteractionrandomizedcontrolledtrial AT yuvalsilberman intranasalinsulinforthetreatmentofalcoholusedisorderdesignandmethodologyofanalcoholinteractionrandomizedcontrolledtrial AT robertmswift intranasalinsulinforthetreatmentofalcoholusedisorderdesignandmethodologyofanalcoholinteractionrandomizedcontrolledtrial AT leahrhanson intranasalinsulinforthetreatmentofalcoholusedisorderdesignandmethodologyofanalcoholinteractionrandomizedcontrolledtrial AT williamhfreyii intranasalinsulinforthetreatmentofalcoholusedisorderdesignandmethodologyofanalcoholinteractionrandomizedcontrolledtrial |