A Novel Compound for Alcoholism Treatment: A Translational Strategy

• Status: Completed
• Trial end date: 2020-09-09
• Target enrollment: 0
• Participant gender: All

Summary

Background:

Hormones are naturally occurring chemicals in the body. Ghrelin is a hormone that stimulates appetite. It may also stimulate alcohol cravings and use. Researchers want to learn more about alcohol cravings and test if a drug that blocks ghrelin lowers alcohol cravings.

Objective:

To test if the drug PF-05190457 decreases alcohol craving.

Eligibility:

People ages 18-70 who have:

Alcohol use disorder

No other serious medical problems

Woman must be postmenopausal or have had surgery to prevent pregnancy.

Design:

Participants will stay on the inpatient unit here at the Clinical Center for two 2-week stages, which will be separated by at least 2 days. The inpatient phase include:

Taking the study drug or placebo by mouth twice daily

Blood tests

Tasting several sweet solutions

Physical exams

Smokers will smoke cigarettes through a device that gives information about how they smoke a

cigarette.

Exposure to alcohol, water, and food cues in a bar-like room. Participants answer questions on a computer.

Blood pressure and heart rate are monitored through an arm cuff and sensors on the chest. Saliva is collected

through cotton rolls in the mouth.

MRIs: Participants lie on a table that slides in and out of the cylinder, and a coil is placed over the head.

They complete tasks on a computer screen while in the cylinder. This lasts up to 2 hours.

Wearing a virtual reality headset, walking around a virtual room, and selecting virtual food and drink.

Participants will have 8 hour long follow-up visits in our Outpatient Clinic These include:

Counseling to abstain from alcohol use. Sessions may be videotaped.

Physical exams

...

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Criteria

• INCLUSION CRITERIA:

• Male or female individuals 18-70 years old (inclusive)

• Current Alcohol Use Disorder (AUD) by DSM-5 criteria based on the SCID

• Most recent urine drug test for illegal drugs of abuse is negative

• Most recent Clinical Institute Withdrawal Assessment for Alcohol - revised (CIWA-Ar) score is less than or equal to 8

• Heart rate less than or equal to 100 on two separate measurements, both assessed after CIWA-Ar score is less than or equal to 8

• Female subjects must be of non childbearing potential as defined by at least one of the following criteria:

a) Females 45-70 years old, who are menopausal, defined as follow:

i) Females who are between 45-55 years old: they will be considered menopausal if they satisfy all the following three requirements during screening: 1) they are in amenorrhea, defined as absence of menstruation for the previous 12 months; 2) they have a negative urine pregnancy test; and 3) they have a serum FSH level within the laboratory s reference range for postmenopausal females.

ii) Females who are between 56-70 years old: they will be considered menopausal if they are in amenorrhea, defined as absence of menstruation for the previous 12 months before screening.

OR

b) Females 21-70 years old, who have a documented hysterectomy and/or bilateral oophorectomy.

All other female subjects (including females with tubal ligations and females that do NOT have a documented hysterectomy) will be considered to be of childbearing potential.

• Male subjects must use one of the following methods of contraception from the first dose of study medication and until 28 days after dosing (given that it is unknown whether the effects of this drug can cause birth defects):

1. Abstinence.

2. A condom AND one of the following:

• Vasectomy for more than 6 months.

• Female partner who meets one of the following conditions:

1. Has had a tubal ligation, hysterectomy, or bilateral oophorectomy;

2. Is post menopausal;

3. Uses one of the following forms of contraception:

Copper or hormonal containing IUD;

Spermicidal foam/gel/film/cream/suppository;

Diaphragm with spermicide;

Oral contraceptive;

Injectable progesterone;

Subdermal implant.

EXCLUSION CRITERIA:

• Lifetime clinical diagnosis of schizophrenia or bipolar disorder

• EKG with QTc > 450 msec as determined by the Fridericia formulas.

• BMI less than or equal to 18.5 kg/M(2) or anorexia

• BMI greater than or equal to 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).

• Most recent blood tests show creatinine greater than or equal to 2 mg/dL, AST or ALT > 3 times the upper normal limit, hemoglobin <10.5 g/dl

• Subjects who have diabetes and/or are treated with any drug with glucose lowering properties such as sulfonylurea, insulin, metformin, thiazolidinediones (TZD), Dipeptidyl peptidase-4 (DPP4) inhibitors, or Glucagon-like peptide-1(GLP-1)agonists (due to the glucose-lowering properties of PF-05190457 observed in healthy volunteers)

• Exclusionary Medications:

• A. Naltrexone, acamprosate, alcohol dehydrogenase inhibitors, topiramate, gabapentin, ondansetron, benzodiazepines, baclofen, drugs that are known to prolong the QTc interval and barbiturates as well as hormone replacement therapy; medications and dietary/herbal supplements (like St. John's wort) that interact with Cytochrome P450 3A4. Patients who take these medications may be enrolled in the study only if the potentially interacting medication has been stopped for a period of at least 5 half-lives of the interacting medication before PF-05190457 administration. Patients who take these medications on an as needed (PRN) schedule or take

the medication as a one-time dose as part of a medical procedure or a diagnostic test, for example, may not have to wait the 5 half-lives period of time before enrollment; this will be evaluated on a case by case basis by the MAI and/or PI, based on the specific pharmacological properties of the medication.

• Unable to pass a finger rub hearing test

• Vision is unable to be corrected to (Snellen) 20/100

• Clinically-significant history of motion or car sickness, or history of vestibular disorders

• Any other reason or clinical condition for which the PI or the MAI will consider unsafe for a possible participant to participate in this study

EXCLUSION CRITERIA FOR fMRI ONLY:

• Have contraindications for brain fMRI, as determined by the NIAAA MRI Safety screening form (conducted under the 14-AA-0181 Screening Protocol)

• Colorblindness (this would prevent subject from completing the Stroop task) using the Ishihara Test for Color Deficiency, Concise Edition, 2014.