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AlcoholismPhase 2NCT02707055

A Novel Compound for Alcoholism Treatment: A Translational Strategy - Part II

A Phase 2 study testing PF-05190457 in people with Alcoholism, run by National Institute on Alcohol Abuse and Alcoholism (NIAAA) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Alcoholism
What is being tested?
PF-05190457
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
42 participants
Where
1 siteUnited States
Study dates
15 Jun 2016to 9 Sep 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • Females 45-70 years old, who are menopausal, defined as follow:
  • 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.
  • 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
  • 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):
  • Abstinence.
  • A condom AND one of the following:
  • Vasectomy for more than 6 months.
  • Female partner who meets one of the following conditions:
  • Has had a tubal ligation, hysterectomy, or bilateral oophorectomy;
  • Is post menopausal;
  • 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.

Who cannot join

  • 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).
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  • 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
  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

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.

Read more

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

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.

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.

Physical exams

Read the detailed description

Objective:

Ghrelin is a 28-amino acid peptide that stimulates appetite and food intake. It is an endogenous ligand for the growth hormone secretagogue receptor (GHSR1a). Preclinical studies suggest that ghrelin modulates alcohol reward processing. Previous work from our research team, indicated that intravenous (IV) ghrelin administration, compared to placebo, results in an acute increase in alcohol craving during a cue-reactivity experiment in alcoholic individuals. Therefore, an oral bioavailable, ghrelin receptor antagonist that is able to pass through the blood brain barrier holds particular promise as a treatment for alcohol use disorder (AUD). This protocol is part of a grant project funded by National Center for Advancing Translational Sciences (NCATS) aimed to generate preliminary evidence in AUD on the safety and efficacy of a ghrelin receptor (GHSR1a) antagonist, PF-05190457, an existing molecule available under the NIH-Industry Pilot Program at NCATS. Completed preclinical and clinical (Protocol #14-AA-0042) work has demonstrated the safety of PF-05190457/alcohol interaction. The goal of this protocol is to conduct a proof-of-concept human laboratory study to assess an early-signal of efficacy of PF-05190457 in AUD.

Study population:

The study population will be AUD individuals (n = 55).

Study Design:

A within-subject, counterbalanced, double-blind, placebo-controlled study.

Outcome measures:

The primary aim will be to determine whether PF-05190457, compared to placebo, reduces alcohol cue-elicited craving. As another outcome will be to determine whether PF-05190457, compared to placebo, reduces brain blood oxygen level dependent (BOLD) response during exposure to alcohol cues, during a task-based fMRI scan. We will also investigate the effects of PF-05190457 on food craving as well as on food choices using a virtual buffet experimental procedure. All these outcomes will be assessed in the inpatient Unit at the NIH Clinical Center (CC). After the inpatient portion of the protocol, patients will be followed-up as outpatients. During the outpatient phase, patients will be offered motivational interviewing and video feedback to explore the effects of this intervention, compared to supportive counseling, on maintaining motivation for alcohol abstinence and inform future studies where medications like PF-05190457 and behavioral treatments may be combined. The outpatient phase is optional for treatment seeking and nontreatment seeking participants.

Conditions
Alcoholism
Being tested
PF-05190457, Placebo
Keywords
Alcohol Consumption, Alcohol Treatment, Alcoholism, Ghrelin, Ghrelin Antagonism
Medical subject headings
Alcoholism, Alcohol Drinking

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PF-05190457Drug

    Ghrelin Receptor Inverse Agonist

  • PlaceboOther

    Placebo

Study groups in NCT02707055
Study groupRoleWhat they receive
PF-05190457, then placeboExperimentalParticipants with alcohol use disorder received PF-05190457 100 mg twice a day for a maximum of 14 days followed by a minimum of 2-day washout period, then placebo twice a day for a maximum of 14 days.
Receives: Drug: PF-05190457; Other: Placebo
Placebo, then PF-05190457Placebo comparatorParticipants with alcohol use disorder received placebo twice a day for a maximum of 14 days followed by a minimum of 2-day washout period then PF-05190457 100 mg twice a day for a maximum of 14 days.
Receives: Drug: PF-05190457; Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: 96 minutes

Secondary outcomes (1)

  1. Food Choices in a "Virtual Buffet" Conducted in a Virtual Reality Context.

    Food choice was assessed by calculating the total of number of calories for a meal selected in a virtual buffet environment. Calories were adjusted for the size of items in the virtual reality environment.

    Measured: 40 minutes

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Mar 2016 (estimated)
  2. Study start15 Jun 2016
  3. Primary completion20 Feb 2020
  4. Study completion9 Sep 2020

Why it stopped: Early termination of the study due to the COVID-19 pandemic

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Crossover
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02707055
Sponsor's protocol ID
160080
Other IDs
16-DA-0080
Status last verified
Oct 2021
First submitted
11 Mar 2016
Last updated
16 Mar 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Tyler RE, Pfaff RK, Khan RMN, Loften A, Zurick R, Zeng Y, Arisa OT, Harvey C, Akhlaghi F, Figg WD, Farokhnia M, Leggio L. Pharmacokinetic and pharmacodynamic results from a randomized controlled study with the growth hormone secretagogue receptor blocker PF-5190457 in recently abstinent patients with alcohol use disorder. Int J Neuropsychopharmacol. 2026 Feb 2;29(2):pyaf081. doi: 10.1093/ijnp/pyaf081.

    PubMed 41474196

  • Faulkner ML, Farokhnia M, Lee MR, Farinelli L, Browning BD, Abshire K, Daurio AM, Munjal V, Deschaine SL, Boukabara SR, Fortney C, Sherman G, Schwandt M, Akhlaghi F, Momenan R, Ross TJ, Persky S, Leggio L. A randomized, double-blind, placebo-controlled study of a GHSR blocker in people with alcohol use disorder. JCI Insight. 2024 Dec 20;9(24):e182331. doi: 10.1172/jci.insight.182331.

    PubMed 39704175

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing PF-05190457 in people with Alcoholism, run by National Institute on Alcohol Abuse and Alcoholism (NIAAA) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 16 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Alcohol Cue-elicited Craving Assessed in a "Bar-like" Laboratory (time frame: 96 minutes). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02707055, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2022; AzTrials last refreshed its copy on 7 Nov 2026.

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