GOAT

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.

Bariatric surgery helps patients with severe obesity to lose weight, cures and prevents diseases linked to obesity and reduces the risk of death. Unfortunately, 1 in 5 patients do not respond well to surgery in terms of weight loss and health gains. Thus, maximising weight loss and health benefits after surgery is critical. This study aims to gain insight into the role that the appetite-stimulating hormone, ghrelin, plays in driving appetite and energy intake in patients with poor weight loss (≤ 20% total body weight) following bariatric surgery. This will guide future work to develop pharmacological treatments for obesity, both as standalone treatments and adjuncts to bariatric surgery.
Participants will be invited to attend the Clinical Research Facility at University College London Hospital for a screening visit and six study visits. Active ghrelin levels will be reduced by inhibiting ghrelin-o-acyl-transferase (GOAT), the enzyme needed to generate active ghrelin (acyl ghrelin, AG). Participants will be randomised to receive GLWL-01 (GOAT inhibitor) 300mg BD or placebo for a 10 day study cycle. The effect of AG reduction on appetite and energy intake will be evaluated through both fixed-energy and ad libitum meal tests on day 7 and 10, respectively. Measures of body weight and composition, appetite and food cravings will be performed in addition to biochemical profiling of circulating gut hormone, adipokine and cytokine levels. Targeted physical examinations and assessment of adverse events will be performed. Safety monitoring calls will be conducted 2 and 7 days after the last dose. Following a 6-10 week washout period, participants will cross over to receive either placebo or GLWL-01 300mg BD and undergo a second study cycle, with all measures repeated.

The aim of this study is to evaluate efficacy, safety, and pharmacokinetics of GLWL-01 in the treatment of patients with Prader-Willi Syndrome (PWS).