Manipulating Ghrelin Signaling Via GOAT Inhibition in Alcohol Use Disorder

NCT03896516 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 99991907519-DA-N075
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

Background: People with alcohol use disorder (AUD) have trouble controlling their drinking. Medications can help some people with AUD but are not effective for many others. Researchers want to test new drugs to better treat the disease. Objective: To see if the investigational drug GLWL-01 is safe to use in people with alcohol problems. Also, to find out if the drug reduces the urge to drink alcohol. Eligibility: People ages 18-70 with Alcohol Use Disorder (AUD) Design: Participants will be screened under protocol 06-DA-N415. Participants will be admitted to the inpatient facility, Clinical Research Unit (CRU) on the Johns Hopkins Bayview Medical Center for up to 21 days. They may leave the CRU on specified days pending approval. All their meals will be provided. They cannot drink alcohol. Participants will take either the study drug or a placebo by mouth twice daily. They will not know which they are receiving. Participants will complete many questionnaires. Participants may have urine tests. Participants will complete tasks on a computer. Participants will have blood samples obtained on some study days. Participants will taste and indicate their preference for sweet liquids. Participants' blood pressure, pulse, respiratory rate, body temperature and weight, heart rate and rhythm will be measured. Participants will have breath testing to obtain information about smoking. Participants will be exposed to alcohol cues, water, and food cues in a bar-like room. Cues are things that might make them feel the urge to eat or drink alcohol. Participants will take part in a virtual buffet experiment - They will wear a virtual reality headset, walk around a virtual room, and select virtual food and drink.

Conditions

Alcohol Use Disorder

Keywords

Alcohol Problems; Alcohol Craving; Food-Seeking Behaviors; Ghrelin; Ghrelin O-acyltransferase

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Adverse Events (AEs)

  Number of participants with adverse events related to intervention. Adverse events were collected from participants self reporting.

  Up to one month

• Alcohol Cue-elicited Craving Assessed in a "Bar-like" Laboratory

  Alcohol cue elicited craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value). Higher score indicated higher alcohol craving. AUQ was collected on each initial dosing days (2-3 days), the virtual reality buffet day (1 day), the cue-reactivity day (1 day), and the final study day (1 day), for a total of 5-6 days per intervention. The least squares average for each intervention was calculated using a linear mixed effects model including a random intercept for each participant.

  AUQ scores were collected 5-6 days per intervention [initial dosing days (2-3 days), the virtual reality buffet day (1 day), the cue-reactivity day (1 day), and the final study day (1 day)]

Study Arms (2)

GLWL-01, then Placebo

EXPERIMENTAL

Participants receive GLWL-01 450 mg orally twice daily for a minimum of four days (Stage I) followed by a minimum of two day wash-out period then placebo orally twice daily for a minimum of four days (stage II).

Other: Placebo; Drug: GLWL-01

Placebo, then GLWL-01

PLACEBO COMPARATOR

Participants receive placebo orally twice daily for a minimum of four days (Stage I) followed by a minimum of two day wash-out period then GLWL-01 450 mg orally twice daily for a minimum of four days (stage II).

Other: Placebo; Drug: GLWL-01

Interventions

Placebo OTHER

Participants receive Placebo orally twice daily.

GLWL-01, then Placebo; Placebo, then GLWL-01

GLWL-01 DRUG

GLWL-01 is a ghrelin O-acyltransferase (GOAT) inhibitor. Participants receive GLWL-01 orally twice daily.

GLWL-01, then Placebo; Placebo, then GLWL-01

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Alcohol Use Disorder (Minimum 2 symptoms on a validated diagnostic tool e.g., the Mini-International Neuropsychiatric Interview (MINI) or the Structured Clinical Interview for DSM Disorders (SCID)
• Male or female individuals 18-70 years old (inclusive)
• Able to speak, read, write and understand English
• Most recent urine drug test for benzodiazepines, barbiturates, cocaine metabolites, morphine, oxycodone, methadone, amphetamine, \& buprenorphine is negative.
• Most recent Clinical Institute Withdrawal Assessment for Alcohol - revised (CIWA-Ar) score is less than or equal to 8
• Males only:
• Males agrees agree to sexual abstinence or to use a reliable method of birth control during the study and three months following the last dose of the study drug. Acceptable methods of birth control may include: 1) condom with spermicide; 2) diaphragm with spermicide; or 3) female condom with spermicide.
• Females only:
• Women of child-bearing potential may participate in the study:
• if they test negative for pregnancy (based on a urine pregnancy test) prior to initiation of treatment
• they must also agree to use either one highly effective method of contraception or a combination of two effective methods of contraception during the study.
• Highly effective method may include hormonal contraceptives (e.g., combined oral contraceptives, patch, vaginal ring, injectables, and implants); intrauterine device or/ intrauterine system; vasectomy and tubal ligation.
• Effective methods may include barrier methods of contraception (e.g., male condom, female condom, cervical cap, diaphragm, contraceptive sponge)
• Women may choose to use a double-barrier method of contraception. Barrier methods without concomitant use of a spermicide are not reliable or an acceptable method. Thus, each barrier method must include use of a spermicide. It should be noted that the use of male and female condoms as a double-barrier method is not considered acceptable due to the high failure rate when these methods are combined.
• Women not of child-bearing potential may participate in the study and include those who have

You may not qualify if:

• Lifetime clinical diagnosis of schizophrenia or bipolar disorder
• BMI \< 18.5 kg/m(2) and weight less than 60 Kg (both must be met)
• BMI \>= 40 kg/m(2)
• History of epilepsy and/or seizures
• NOTE: individuals who have a history of alcohol withdrawal seizures may be in the study as long as they have been abstinent from alcohol for at least 2 weeks prior to consent and during that period of abstinence, there were no seizure episodes (otherwise, participant remains not eligible).
• Creatinine greater than or equal to 2 mg/dL, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 1.5 times the upper normal limit, hemoglobin \<10.5 g/dl
• Diagnosis of liver cirrhosis
• Clinically significant history or current eating, pituitary or adrenal gland disorders or disorder of gastric motility as judged by a study clinician as determined from medical history and/or current clinical screening information
• Current thyroid disorders that are not stable on dose of FDA-approved medications for that disease, as judged by a study clinician as determined from medical history and/or current clinical screening information. A pre-existing stable medical condition is defined as a disease not requiring significant change in therapy or hospitalization for worsening disease during the past 3 months.
• Clinically significant abnormal 12-Lead ECG
• QTcF \> 450 msec for men and \> 470 msec for women
• Family history of Long QT Syndrome.
• Patients on weight loss medications within 30 days of dosing
• Patients with a history of bariatric surgery
• Diagnosis of diabetes and currently on medication

Sponsors & Collaborators

• National Institute on Drug Abuse (NIDA): lead

Study Sites (1)

National Institute on Drug Abuse

Baltimore, Maryland, 21224, United States

Location

MeSH Terms

Conditions

Alcoholism; Alcohol-Related Disorders

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr Lorenzo Leggio, M.D., Ph.D.
• Organization: National Institute on Drug Abuse (NIDA)

lorenzo.leggio@nih.gov

1-667-312-5188

Study Officials

• Lorenzo Leggio, M.D.

  National Institute on Drug Abuse (NIDA)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2019
• First Posted: April 1, 2019
• Study Start: June 22, 2021
• Primary Completion: December 4, 2023
• Study Completion: December 4, 2023
• Last Updated: January 15, 2025
• Results First Posted: January 15, 2025

Record last verified: 2024-03-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Twelve months after publication
• Access Criteria: To be determined.

Locations

US (1)