Alcohol DrinkingPhase 2TOPMRINCT02074904
Topiramate's Effects on Heavy Drinking
A Phase 2 study testing Topiramate in people with Alcohol Drinking, run by University of Pennsylvania at 1 site in United States.
Trial summary
The proposed project will utilize perfusion functional magnetic resonance imaging (fMRI) to examine the effects of topiramate on brain and behavioral responses in heavy drinkers to appetitive alcohol reminders (cues that motivate continued alcohol use and relapse). Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Alcohol Drinking
- What is being tested?
- Topiramate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- May 2015to Mar 2017
- 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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Physically healthy, as determined by a comprehensive physical examination and approval of the study physician, males or females who drink alcohol, ages 18-60.
- Average weekly ethanol consumption of >24 standard drinks for men, or >18 standard drinks for women.
- Females must be non-pregnant, non-lactating and either be of non-childbearing potential (i.e. sterilized via hysterectomy or bilateral tubal ligation or at least 2 years postmenopausal) or of child bearing potential but practicing a medically acceptable method of birth control. Examples of medically acceptable methods for this protocol include: the birth control pill, intrauterine device, injection of Depo-Provera, Norplant, contraceptive patch, contraceptive ring, double-barrier methods (such as condoms and diaphragm/spermicide), male partner sterilization, abstinence (and agreement to continue abstinence or to use an acceptable method of contraception, as listed above, should sexual activity commence), and tubal ligation.
- Provide voluntary informed consent.
- Must be able to read. [Subjects are required to be able to read because there are several self-administered measures that they must read, understand and provide written answers.]
- Intelligence quotient of ≥ 80.
Who cannot join
- Current, clinically significant physical disease or abnormality on the basis of medical history, physical examination, or routine laboratory evaluation.
- History of head trauma or injury causing loss of consciousness, lasting more than five (5) minutes or associated with skull fracture or inter-cranial bleeding or abnormal MRI.
- Current major DSM-IV Axis I diagnoses other than alcohol use disorder (except nicotine use disorder).
- Presence of magnetically active irremovable prosthetics, plates, pins, permanent retainer, bullets, etc. (unless a radiologist confirms that it's presence is unproblematic). An x-ray may be obtained to determine eligibility given the possibility of a foreign body.
- History of a serious psychiatric illness including psychosis, bipolar disorder, or suicidal or homicidal intent.
- Current treatment with carbonic anhydrase inhibitors.
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- Claustrophobia or other medical condition preventing subject from lying in the MRI for approximately one (1) hour.
- Current regular treatment with psychotropic medications (e.g., benzodiazepines, antidepressants), which affect neurotransmitter systems or a medication being used to treat alcohol use disorders (e.g., naltrexone, acamprosate).
- Vision problems that cannot be corrected with glasses.
- Body Mass Index (BMI) greater than or equal to 34, body girth greater than 52 inches and a head girth greater than 25 inches.
- History of stroke and/or stroke related spasticity.
- History of glaucoma or kidney stones.
- HIV positive.
- History of seizures.
- History of topiramate treatment for alcohol use disorder and report no treatment response.
- Current DSM-5 diagnosis of alcohol use disorder that is clinically too severe to permit them to participate in a research trial in which the goal is to stop or reduce drinking.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania Center for Studies of Addiction
Philadelphia, Pennsylvania, 19104
About this study
Official title: Brain Mechanisms of Topiramate's Effects on Heavy Drinking
The proposed project will utilize perfusion functional magnetic resonance imaging (fMRI) to examine the effects of topiramate on brain and behavioral responses in heavy drinkers to appetitive alcohol reminders (cues that motivate continued alcohol use and relapse). This project will yield novel findings on brain and behavioral responses to alcohol cues, the effects of topiramate on alcohol cue reactivity, and the mechanisms underlying topiramate's ability to blunt alcohol cue reactivity and heavy drinking.
Read the detailed description
This project is a double-blind, randomized, placebo-controlled study of topiramate's effects on brain and behavior responses in heavy drinkers. Eligible volunteers who meet study criteria will be randomized to receive either topiramate or placebo with weekly visits and medication management sessions. Participants will complete two magnetic resonance imaging sessions. The first scan session will occur prior to starting study drug, and the second scan will occur following six weeks of study drug. This project will yield novel findings on brain and behavioral responses to alcohol cues, the effects of topiramate on alcohol cue reactivity, and the mechanisms underlying topiramate's ability to blunt alcohol cue reactivity and heavy drinking.
- Conditions
- Alcohol Drinking
- Being tested
- Topiramate, Placebo
- Medical subject headings
- Alcohol Drinking
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TopiramateDrug
Also called Topamax
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Topiramate | Experimental | up to 200mg/day orally (over 8 weeks during which the dosage is gradually increased up to 200 mg orally and then maintained, and 1 week of medication taper) Receives: Drug: Topiramate |
| Placebo | Placebo comparator | placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
fMRI Response in the Ventral Striatum/Medial Orbitofrontal Cortex During Alcohol Cue Exposure
At baseline (prior to randomization), brain and behavioral responses will be significantly greater during alcohol cue exposure compared to non-alcohol cue exposure. Following 6 weeks of study drug, individuals receiving topiramate will demonstrate greater reductions in brain activity and drinking behavior compared to individuals receiving placebo. Individuals receiving placebo will exhibit responses similar to baseline responses.
Measured: baseline to after 6 weeks of study drug
Secondary outcomes (4)
Drinking Days
change in drinking days from baseline to 9 weeks
Measured: baseline and 9 weeks
Change in Gamma-glutamyl Transferase (GGT) or Carbohydrate-deficient Transferrin (CDT) Levels
Change in gamma-glutamyl transferase (GGT) or carbohydrate-deficient transferrin (CDT) levels after 9 weeks of treatment.
Measured: baseline and Visit 9 (9 weeks)
Heavy Drinking Days
change in number of heavy drinking days from baseline to 9 weeks
Measured: baseline to 9 weeks
Mean Alcohol Consumption
change in mean alcohol consumption from baseline to 9 weeks
Measured: baseline to 9 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2014 (estimated)
- Study startMay 2015
- Primary completionMar 2017
- Study completionMar 2017
Why it stopped: We terminated the study to run it as a sub-study of NCT02371889, which is a 13 week, placebo controlled, double-blind, trial of topiramate in heavy drinkers.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Alcohol DrinkingStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Reagan R Wetherill, PhD, Principal investigator, University of PennsylvaniaHenry R Kranzler, MD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02074904
- Sponsor's protocol ID
- TOP MRI
- Acronym
- TOPMRI
- Status last verified
- Dec 2017
- First submitted
- 20 Feb 2014
- Last updated
- 21 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Brain Mechanisms of Topiramate's Effects on Heavy Drinking
- ClinicalTrials.gov ID
- NCT02074904
- Acronym / sponsor ID
- TOPMRI / TOP MRI
- Conditions
- Alcohol Drinking
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: We terminated the study to run it as a sub-study of NCT02371889, which is a 13 week, placebo controlled, double-blind, trial of topiramate in heavy drinkers.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- May 2015
- Primary completion
- Mar 2017 (actual)
- Study completion
- Mar 2017 (actual)
- First posted
- 28 Feb 2014 (estimated)
- Results
- Posted 11 Dec 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The proposed project will utilize perfusion functional magnetic resonance imaging (fMRI) to examine the effects of topiramate on brain and behavioral responses in heavy drinkers to appetitive alcohol reminders (cues that motivate continued alcohol use and relapse). This project will yield novel findings on brain and behavioral responses to alcohol cues, the effects of topiramate on alcohol cue reactivity, and the mechanisms underlying topiramate's ability to blunt alcohol cue reactivity and heavy drinking.
Detailed description
This project is a double-blind, randomized, placebo-controlled study of topiramate's effects on brain and behavior responses in heavy drinkers. Eligible volunteers who meet study criteria will be randomized to receive either topiramate or placebo with weekly visits and medication management sessions. Participants will complete two magnetic resonance imaging sessions. The first scan session will occur prior to starting study drug, and the second scan will occur following six weeks of study drug. This project will yield novel findings on brain and behavioral responses to alcohol cues, the effects of topiramate on alcohol cue reactivity, and the mechanisms underlying topiramate's ability to blunt alcohol cue reactivity and heavy drinking.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Topiramate | Experimental | Drug: Topiramateup to 200mg/day orally (over 8 weeks during which the dosage is gradually increased up to 200 mg orally and then maintained, and 1 week of medication taper) |
| Placebo | Placebo comparator | Drug: Placeboplacebo |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Physically healthy, as determined by a comprehensive physical examination and approval of the study physician, males or females who drink alcohol, ages 18-60.
- Average weekly ethanol consumption of >24 standard drinks for men, or >18 standard drinks for women.
- Females must be non-pregnant, non-lactating and either be of non-childbearing potential (i.e. sterilized via hysterectomy or bilateral tubal ligation or at least 2 years postmenopausal) or of child bearing potential but practicing a medically acceptable method of birth control. Examples of medically acceptable methods for this protocol include: the birth control pill, intrauterine device, injection of Depo-Provera, Norplant, contraceptive patch, contraceptive ring, double-barrier methods (such as condoms and diaphragm/spermicide), male partner sterilization, abstinence (and agreement to continue abstinence or to use an acceptable method of contraception, as listed above, should sexual activity commence), and tubal ligation.
- Provide voluntary informed consent.
- Must be able to read. [Subjects are required to be able to read because there are several self-administered measures that they must read, understand and provide written answers.]
Key exclusion criteria (16 listed)
- Current, clinically significant physical disease or abnormality on the basis of medical history, physical examination, or routine laboratory evaluation.
- History of head trauma or injury causing loss of consciousness, lasting more than five (5) minutes or associated with skull fracture or inter-cranial bleeding or abnormal MRI.
- Current major DSM-IV Axis I diagnoses other than alcohol use disorder (except nicotine use disorder).
- Presence of magnetically active irremovable prosthetics, plates, pins, permanent retainer, bullets, etc. (unless a radiologist confirms that it's presence is unproblematic). An x-ray may be obtained to determine eligibility given the possibility of a foreign body.
- History of a serious psychiatric illness including psychosis, bipolar disorder, or suicidal or homicidal intent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TopiramateAlso: Topamax | Drug | Topiramate |
| Placebo | Drug | Placebo |
Primary outcome
fMRI Response in the Ventral Striatum/Medial Orbitofrontal Cortex During Alcohol Cue Exposure
Time frame: baseline to after 6 weeks of study drug
At baseline (prior to randomization), brain and behavioral responses will be significantly greater during alcohol cue exposure compared to non-alcohol cue exposure. Following 6 weeks of study drug, individuals receiving topiramate will demonstrate greater reductions in brain activity and drinking behavior compared to individuals receiving placebo. Individuals receiving placebo will exhibit responses similar to baseline responses.
4 secondary outcomes
Drinking Days
Time frame: baseline and 9 weeks
Change in Gamma-glutamyl Transferase (GGT) or Carbohydrate-deficient Transferrin (CDT) Levels
Time frame: baseline and Visit 9 (9 weeks)
Heavy Drinking Days
Time frame: baseline to 9 weeks
Mean Alcohol Consumption
Time frame: baseline to 9 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Reagan R Wetherill, PhD principal investigator
University of Pennsylvania
Henry R Kranzler, MD principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Topiramate in people with Alcohol Drinking, run by University of Pennsylvania 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 6 inclusion and 16 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 21 Sep 2018. 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 11 Dec 2017). 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?
fMRI Response in the Ventral Striatum/Medial Orbitofrontal Cortex During Alcohol Cue Exposure (time frame: baseline to after 6 weeks of study drug). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 21 Sep 2018.