Ghrelin Signaling Via GOAT Inhibition in Alcohol Use Disorder
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03896516|
Recruitment Status : Not yet recruiting
First Posted : April 1, 2019
Last Update Posted : August 22, 2019
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.
To see if the 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.
People ages 18-70 who are seeking treatment for AUD
Participants will be screened under protocol 14-AA-00181.
Participants will be admitted to the NIH Clinical Center for up to 32 days. They may leave the hospital some of the time. 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 tests each day.
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.
|Condition or disease||Intervention/treatment||Phase|
|Alcohol Use Disorder||Drug: GLWL-01 Other: Placebo||Phase 1 Phase 2|
Hide Detailed Description
Background and Objective:
Acyl-ghrelin is a 28-amino acid peptide that stimulates appetite and food intake. It is an endogenous ligand for the growth hormone secretagogue receptor (GHS-R1a). Preclinical studies suggest that acyl-ghrelin increases alcohol intake (Szulc, Mikolajczak et al. 2013, Cepko et al. 2014) and decreases in acyl-ghrelin and GHS-R1a function suppresses alcohol consumption (Kaur and Ryabinin 2010, Landgren et al. 2012, Bahi et al. 2013, Suchankova et al. 2013, Gomez and Ryabinin 2014, Suchankova, Engel et al. 2016 Furthermore, previous human studies indicate a positive correlation between endogenous ghrelin levels and alcohol craving and drinking (Addolorato, Capristo et al.2006). In clinical studies conducted by our group with individuals with AUD, intravenous (IV) acyl-ghrelin administration, versus placebo 1) increased alcohol craving during alcohol cue-exposure and 2) increased IV alcohol self-administration as well as decreased latency to first infusion of alcohol and 3) increased brain activation in the amygdala in anticipation of alcohol reward. Together, this preclinical and human data suggest that manipulating the ghrelin signal may be a novel and potentially effective pharmacological approach to treat individuals with alcohol use disorder.
After the discoveries of GHS-R1a and acyl-ghrelin, a next step was identifying ghrelin O-acyltransferase (GOAT) the enzyme that catalyzes the conversion of des-acyl-ghrelin (DAG) to acyl-ghrelin via octanoylation. GOAT is thus the master switch for the ghrelin system , as acyl-ghrelin, not DAG, is biologically active at the GHSR-1a. GOAT s structure is highly conserved, is produced by endocrine cells in the stomach and is co-expressed with ghrelin. Therefore, GOAT is a promising target for manipulating the ghrelin system by altering the peripheral acyl-to-total ghrelin ratio (where total ghrelin = acyl-ghrelin + DAG). Recently, the ghrelin system has been investigated as a potential treatment target for AUDs. As such, an oral bioavailable GOAT inhibitor offers encouraging potential as a treatment for alcohol use disorder. GLWL-01 is an existing GOAT inhibitor for which GLWL Research Inc. has recently and successfully completed a first-in-human safety clinical trial. The goal of this protocol is to conduct a proof-of-concept human laboratory study to assess a potential early signal of efficacy of GLWL-01 in relation to alcohol-related outcomes.
Males and females (N = 43) with alcohol use disorder.
A within-subject, counterbalanced, double-blind, placebo-controlled study. Participants will take GLWL-01 450 mg b.i.d. or matched placebo for a minimum of 7 days (Stage I). After a wash-out window, Stage II will take place during which the counterbalanced study drug will be administered for a minimum of 7 days.
Primary outcome measure:
The co-primary aims will be to determine whether: 1) the number of adverse events (AEs) experienced differ in the GLWL-01 condition, compared to placebo; and 2) GLWL-01, compared to placebo, reduces alcohol cue-elicited craving using a validated alcohol cue-reactivity procedure.
Secondary outcome measures:
The main secondary aim will be the effects of GLWL-01 on food choices using a virtual buffet experimental procedure. We will also monitor a wide range of behavioral measures including e.g., pain, anxiety, depression, alcohol craving and withdrawal, and smoking.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||43 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Double (Participant, Care Provider)|
|Official Title:||Manipulating Ghrelin Signaling Via GOAT Inhibition in Alcohol Use Disorder|
|Estimated Study Start Date :||August 27, 2019|
|Estimated Primary Completion Date :||November 26, 2020|
|Estimated Study Completion Date :||November 26, 2020|
Experimental: Active Drug
Participants will take GLWL-01 450 mg b.i.d. or matched placebo for up to 16 days (Stage I). After a wash-out window, Stage II will take place during which the counterbalanced study drug will be administered for up to 16 days.
Placebo Comparator: Placebo
Participants will take GLWL-01 450 mg b.i.d. or matched placebo for up to 16 days
- Primary outcome mesure: to determine whether: 1) the number of adverse events (AEs) experienced differ in the GLWL-01 condition, compared to placebo; and 2) GLWL-01, compared to placebo, reduces alcohol cue-elicited craving using validated cue-r... [ Time Frame: 1-year ]The co-primary aims will be to determine whether: 1) the number of adverse events (AEs) experienced differ in the GLWL-01 condition, compared to placebo; and 2) GLWL-01, compared to placebo, reduces alcohol cue-elicited craving using a validated alcohol cue-reactivity procedure.
- The effects of GLWL-01 on food choices using a "virtual buffet" experimental procedure. We will also monitor a wide range of behavioral measures including e.g., pain, anxiety, depression, alcohol craving, withdrawal, smoking [ Time Frame: 1-year ]The main secondary aim will be the effects of GLWL-01 on food choices using a "virtual buffet" experimental procedure. We will also monitor a wide range of behavioral measures including e.g., pain, anxiety, depression, alcohol craving and withdrawal, and smoking
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03896516
|Contact: Lisa A Farinelli, R.N.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center||Not yet recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 firstname.lastname@example.org|
|Principal Investigator:||Lorenzo Leggio, M.D.||National Institute on Alcohol Abuse and Alcoholism (NIAAA)|