AzTrials
AzTrials

Alcohol Use DisorderPhase 2NCT02354703

Pharmacogenetic Study of Ondansetron in Alcohol Use Disorder

A Phase 2 study testing Ondansetron in people with Alcohol Use Disorder, run by University of Maryland, Baltimore at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The primary study objective is to determine the efficacy of ondansetron (0.33 mg twice daily) administered orally for a period of 16 weeks in reducing risky drinking among currently drinking subjects with alcohol use disorder who have selected genotypes at the serotonin transporter and receptor genes. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Alcohol Use Disorder
What is being tested?
Ondansetron
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
293 participants
Where
3 sitesUnited States
Study dates
Aug 2015to 31 Mar 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

  • Men and women who have given written informed consent
  • Aged 18 to 70
  • The subject has a breath alcohol concentration (BrAC) = 0.00% at the screening visit and < or = 0.02% at all visits after the screening visit
  • Diagnosis of alcohol use disorder (AUD) using Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria
  • Able to provide Time-Line Follow-Back (TLFB) alcohol consumption information for the 90-day period prior to the Screen Visit.
  • During the 4 weeks preceding the Baseline Visit, the subject reports:
Show all 19Show fewer
  • ≥6 Heavy Drinking Days (HDDs) - defined as a day with alcohol consumption of ≥5 standard drinks (i.e., 12 g of ethanol) for men, and ≥ 4 standard drinks for women
  • ≤14 consecutive abstinent days
  • Total alcohol consumption of an average of ≥21 standard drinks/week for men and ≥14 standard drinks/week for women in past 28 days and have met these criteria during the 7 days prior to randomization
  • An expressed wish to reduce or stop drinking
  • Willingness to participate in behavioral and medicinal treatments for AUD
  • Stable residence in the 28 days prior to the Baseline Visit and no plans to move in the next 9 months. A stable residence is a domicile in which an individual can operate as if it were his or her own homestead and does not include shelters or halfway houses.
  • Provides contact information for 1 or 2 "locators" who can be used to contact the subject
  • Able to read and understand English and complete the rating scales and questionnaires accurately, follow instructions, and make use of the behavioral treatments. This will be assessed with the Slosson Oral Reading Test-Revised, on which the subject must demonstrate at least a 6th grade reading level.
  • If the subject is a woman of child-bearing age, she must:
  • Agree not to try to become pregnant during the study, and use adequate contraception (defined as oral/ systemic contraception, intrauterine device, diaphragm in combination with spermicide, or condom for male partner in combination with spermicide) or
  • Be postmenopausal, (i.e., have had her last natural menstruation at least 24 months prior to baseline) or
  • Have had a hysterectomy or been surgically sterilized prior to the Baseline Visit, or
  • Plan not to be sexually active vaginally with men during the entire duration of the trial.

Who cannot join

  • A subject presenting with any of the following at the Baseline Visit will be excluded from the study:
  • The subject has fewer than 6 heavy drinking days (HDD) (defined as ≥5 standard drinks for men and ≥4 or greater standard drinks for women) in the 4 weeks preceding the Baseline Visit.
  • The subject has greater than 14 consecutive abstinent days in the 4 weeks preceding the Baseline Visit.
  • The subject has a Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-Ar), Revised, score ≥10
  • The subject has a current diagnosis of schizophrenia, bipolar disorder, or other psychotic disorder, or a non-psychotic diagnosis such as major depressive disorder, post-traumatic stress disorder, panic disorder, eating disorder, or substance use disorder (except alcohol, tobacco, or cannabis) that is judged by the PI or designee as exclusionary.
  • Current or recent (within 4 weeks prior to Baseline Visit) treatment with antipsychotics or any medication likely to interact with ondansetron to produce an adverse effect, as judged by a study physician.
Show all 27Show fewer
  • Treatment with any investigational medicinal product within 30 days or 5 half-lives (whichever is longer) prior to Randomization.
  • Currently participating or has recently (4 weeks prior to Randomization) participated in a treatment program for alcohol use disorders.
  • Mini-International Neuropsychiatric Interview (MINI) 6.0 Suicide Risk Assessment module B will be used to assess subjects' risk of suicide. A score of > or = 9 will be evaluated by the PI or designee to determine eligibility. Subjects who are deemed by the PI or designee to be at risk of suicide will be excluded.
  • Clinically significant, unstable physical illness (e.g., hematologic, hepatic or renal insufficiency, or a cardiovascular, pulmonary, gastrointestinal, endocrine, neurological, infectious, neoplastic, or metabolic disturbance), as judged by the PI or designee to be exclusionary
  • Clinically significant abnormal vital signs, as judged by the PI or designee
  • Clinically significant abnormal 12-lead ECG at the Screen Visit, clinically significant cardiovascular disease requiring regular or intensive clinical monitoring, a current history of arrhythmias, or a current or past history of clinically significant QT prolongation, including: QTcF > 450 ms (average of 3 12-lead measurements)
  • Serum potassium, magnesium or calcium levels outside the central laboratory's reference range that are deemed clinically significant by the PI or designee.
  • Taking medications (within the last 7 days prior to the Baseline Visit) that have the potential to prolong the QT interval, as judged by a study physician, or may require such medications during the course of the study. For patients taking these medications, a study physician will evaluate the potential for ondansetron to interact with the medication to produce a clinically significant risk for the participant.
  • Clinically unstable cardiac disease, including unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, active myocardial ischemia or indwelling cardiac pacemaker
  • Complete left bundle branch block
  • History of Long QT Syndrome or a first-degree biological family member with this condition
  • Evidence of hepatic failure and/or ascites, prolonged prothrombin time (International Normalized Ratio [INR] > or = 1.7), bilirubin >10% above the upper limit of the central lab's normal range and/or esophageal variceal disease
  • Active hepatitis and/or serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) or lactate dehydrogenase (LDH) > 3x the upper limit of normal
  • Treatment, either current or within 28 days prior to Randomization, with any medications having a potential effect on alcohol consumption and related behaviors or mood. These include opioid antagonists (e.g., naltrexone, Vivitrol®, Selincro®), glutamate antagonists (e.g., acamprosate), anticonvulsants (e.g., topiramate, gabapentin), serotonin reuptake inhibitors (e.g., fluoxetine), serotonin antagonists (e.g., buspirone), other antidepressants (e.g., tricyclic antidepressants or monoamine oxidase inhibitors), dopamine antagonists (e.g., haloperidol), and disulfiram (Antabuse®)
  • At the Screen Visit, the subject's urine contains opiates, cocaine, amphetamines, barbiturates, or benzodiazepines that cannot be explained by appropriate use of prescribed medication
  • History of severe or life-threatening adverse reactions to ondansetron
  • Female subjects of childbearing potential who have a positive pregnancy test at Baseline Visit or are pregnant, breast feeding, not adhering to an acceptable form of contraception at screening or any time during the study, or unwilling to maintain an acceptable form of contraception throughout the study
  • Prior to Randomization, the subject is compelled to participate in an alcohol treatment program to maintain his/her liberty
  • As of Screen Visit, the subject is sharing a household with a subject randomized to any investigational trial of ondansetron
  • Any other condition or therapy that, in the investigator's opinion, may pose a risk to the subject, prevent the subject from completing the required study procedures or interfere with the study objectives • Less than 75% European ancestry proportions or African-American ancestry proportions
  • Body weight greater than or equal to 110 kg (242 lb)

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • MPRC

    Baltimore, Maryland, 21228

  • University of Pennsylvania Treatment Research Center

    Philadelphia, Pennsylvania, 19103

  • Philadelphia VAMC

    Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 2 Pharmacogenetic Study of Ondansetron in Alcohol Use Disorder

The primary study objective is to determine the efficacy of ondansetron (0.33 mg twice daily) administered orally for a period of 16 weeks in reducing risky drinking among currently drinking subjects with alcohol use disorder who have selected genotypes at the serotonin transporter and receptor genes. The secondary objective is to assess the safety and tolerability of ondansetron in subjects with alcohol use disorder who have selected genotypes at the serotonin transporter and receptor genes.

Read the detailed description

Alcohol use disorder (AUD) is a heterogeneous and chronic relapsing disorder that includes both acute (binge drinking) and chronic (frequent heavy drinking) dimensions. Perhaps because of this heterogeneity, the therapeutic effect size of the approved medicines for the treatment of AUD has been small. In an effort to overcome the heterogeneity of response to a particular medication, recent studies have instituted a personalized approach to therapy. Major breakthroughs in pharmacogenetics have made it possible to identify discrete subgroups of the AUD population according to genetic profiles in order to target the subjects who are most likely to respond to treatment with a particular agent. In addition, genetic variation contributing to the risk of alcohol dependence may be differentially associated with treatment response Thus a successful personalized medicinal approach should ensure that targeted subgroups achieve an optimal treatment response with high predictability. Such an approach holds the potential to identify not only robust responders to treatment but also those who might have minimal or modest adverse effects from the putative therapeutic medication. From a practical clinical standpoint, a personalized medicine approach starts with a genetic screen to identify the "right" subject, who can then be treated with the appropriate medication, with a high probability of a positive treatment outcome and, therefore, a substantial impact on public health.

Being tested
Ondansetron, Placebo
Keywords
alcoholism, treatment, serotonin transporter
Medical subject headings
Alcoholism

What participants receive

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

  • OndansetronDrug

    Ondansetron (0.33 mg) bid+ BBCET counseling

  • PlaceboDrug

    Placebo + BBCET counseling

Study groups in NCT02354703
Study groupRoleWhat they receive
ondansetron-responsive genotypeExperimentalondansetron-0.33 mg bid + Brief Behavioral Compliance Enhancement Treatment (BBCET) for 16 weeks and carrying one of the following genotypes: if European ancestry: SLC6A4 gene: 5-HTTLPR:LL, or rs25531:AA, or 5-HTTLPR + rs25531 (LALA genotype) or rs1042173:TT HTR3A gene: rs1150226:AG; or rs1176713:GG HTR3B gene: rs17619942:AC If African ancestry: HTR3B gene: rs176744: CC or CA SLC6A4 gene: 5-HTTLPR:LL, or rs25531:AA, or 5-HTTLPR + rs25531 (LALA genotype) or rs1042173:TT
Receives: Drug: Ondansetron
ondansetron--non-responsive genotypeExperimentalondansetron-0.33 mg bid + Brief Behavioral Compliance Enhancement Treatment (BBCET) for 16 weeks and NOT carrying any of the responsive genotypes
Receives: Drug: Ondansetron
placebo--responsive genotypePlacebo comparatorplacebo bid + Brief Behavioral Compliance Enhancement Treatment (BBCET) for 16 weeks and carrying one of the following genotypes: if European ancestry: SLC6A4 gene: 5-HTTLPR:LL, or rs25531:AA, or 5-HTTLPR + rs25531 (LALA genotype) or rs1042173:TT HTR3A gene: rs1150226:AG; or rs1176713:GG HTR3B gene: rs17619942:AC If African ancestry: HTR3B gene: rs176744: CC or CA SLC6A4 gene: 5-HTTLPR:LL, or rs25531:AA, or 5-HTTLPR + rs25531 (LALA genotype) or rs1042173:TT
Receives: Drug: Placebo
placebo--non-responsive genotypePlacebo comparatorplacebo bid + Brief Behavioral Compliance Enhancement Treatment (BBCET) for 16 weeks and NOT carrying any of the responsive genotypes
Receives: Drug: Placebo

What is being measured

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

  1. Drinks Per Drinking Day

    self-reported number of standard drinks of alcohol (14 g alcohol) consumed per drinking day

    Measured: 16-week treatment period

Secondary outcomes (2)

  1. Percent Drinking Days

    self-reported percentage of days on which the participant drank alcohol

    Measured: 16-week treatment period

  2. Percent Heavy Drinking Days

    self-reported percentage of days with heavy drinking (at least 5 drinks/day for men, at least 4 drinks/day for women)

    Measured: 16-week treatment period

Timeline

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

  1. First posted3 Feb 2015 (estimated)
  2. Study startAug 2015
  3. Primary completion31 Mar 2020
  4. Study completion31 Mar 2020

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
Treatment
Allocation
Randomised
Intervention model
Factorial
Model description
2 x 2 factorial design: treatment intervention (active, placebo) x genotype (responsive, non-responsive)
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
293 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02354703
Sponsor's protocol ID
HP00061575
Status last verified
Dec 2021
First submitted
23 Jan 2015
Last updated
14 Jan 2022
Data monitoring committee
Yes
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ondansetron in people with Alcohol Use Disorder, run by University of Maryland, Baltimore at 3 sites 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 19 inclusion and 27 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: finished, as of the sponsor's last update on 14 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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 14 Jan 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?

Drinks Per Drinking Day (time frame: 16-week treatment period). 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 NCT02354703.

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 14 Jan 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in