AlcoholismPhase 2NCT00223639
New Medications to Treat Alcohol Dependence
A Phase 2 study testing Topiramate in people with Alcoholism, run by Bankole Johnson at 2 sites in United States.
Trial summary
In the last decade, there has been an explosion of new knowledge of the neuroscientific basis of alcohol-seeking behavior. Briefly, medications that modulate mesolimbic dopamine pathways by facilitating gamma amino butyric function and inhibiting the action of excitatory amino acids should reliably diminish alcohol's… Read more about this study
- Who is it for?
- Ages 21 to 45 years
- Conditions the study is for
- Alcoholism
- What is being tested?
- Topiramate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 29 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 2005to Jul 2008
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 21 to 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- DSM-IV-R diagnosis of alcohol dependence.
- Drinking on average ≥14 and ≥21 drinks/week in the 30 days prior to enrollment for women and men, respectively, and describing a liking for and frequent use of beer as the alcohol-containing beverage.
- Good physical health as determined by a complete physical examination, electrocardiogram within normal limits, and laboratory screening tests within acceptable range (see exclusion criteria).
- Negative pregnancy test at intake. Women of childbearing potential will be placed on oral contraceptives and also will be expected to use barrier and spermicide as an additional form of contraception if sexually active.
- Literate in English language, and able to read, understand, and complete rating scales and questionnaires accurately.
- Willingness to comply with study procedures and protocol including agreement to overnight stay at the human laboratory. Compliance with the alcohol, tobacco, and drug-free environment regulations at the human laboratory is also a condition of enrollment.
- Written informed consent.
Who cannot join
- Expression of desire for immediate treatment for alcohol or drug addiction.
- History of mental illness that warrants treatment or would preclude safe participation in the protocol except nicotine dependence, as determined by mental status and psychiatric interview using the Structured Clinical Interview for DSM-IV.
- Acute or chronic organic brain syndrome, schizophrenia, bipolar disorder, or any psychotic disorder.
- Significant medical illness (including hypertension) as determined by history and/or complete physical examination.
- Uncontrolled uterine or cervical bleeding.
- History of blood clots.
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- Past problems with oral contraceptive pills.
- Gross neurological disease.
- Mental retardation.
- Neurocognitive functioning >1.5 standard deviation below expected range
- Clinically significant abnormalities on the electrocardiogram that will preclude safe participation.
- History of ischemic heart disease or myocardial infarction.
- History of glaucoma or thyroid disease.
- Current infective hepatitis as evidenced by clinical manifestations..
- Positive pregnancy test.
- Women 35 and above who smoke will be excluded from participating in this research study.
- Participation in a human laboratory or clinical study within the last 30 days.
- Clinically significant laboratory screening test (LST) results on hematology, chemistry, or urine analysis as defined by the FDA Neuropharmacology Division guidelines. Elevation of liver enzymes (SGOT), serum glutamic pyruvic transaminase (SGPT), blood urea nitrogen (BUN), or lactate dehydrogenase (LDH) - up to ×4 above the normal range - will be allowed unless there is evidence of hepatocellular disease or failure. In addition, we will test for hematocrit as more than 300 ml of blood will be taken during study 1. Hematocrit levels must be > 41% for males and > 38% for females.
- For study 1, persons weighing less than 110 lbs will be excluded, due to the amount of blood taken in study 1 (more than 300 ml).
- History of any severe or life-threatening reaction to topiramate
- Past or current history of seizures.
- Past or current history of kidney stones.
- Use of any carbonic anhydrase medication.
- Being treated with any medication with potential interactions with alcohol or topiramate.
- Pending imprisonment.
- For smokers, previous adverse reaction to nicotine patch.
- Reporting no experience of craving for alcohol (by self-report).
- Postmenopausal women will not be recruited into this study.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
UVA CARE
Charlottesville, Virginia, 22911
UVA CARE Richmond
Richmond, Virginia, 23294
About this study
In the last decade, there has been an explosion of new knowledge of the neuroscientific basis of alcohol-seeking behavior. Briefly, medications that modulate mesolimbic dopamine pathways by facilitating gamma amino butyric function and inhibiting the action of excitatory amino acids should reliably diminish alcohol's rewarding effects. Topiramate (a sulfamate-substituted fructo-pyranose derivative) has these characteristics. In support of this concept, we have shown in a phase-II-type medications clinical trial that topiramate is significantly superior to placebo at improving drinking outcomes and decreasing craving among (N = 150) alcohol-dependent individuals. Using the carefully controlled environment of the human laboratory, we are submitting a revised application containing a set of systematic studies to assess directly the mechanistic neuropharmacological processes that are associated with topiramate's anti-drinking effects. This will provide a more comprehensive understanding of the neurobiology of alcohol-seeking behavior and aid in the development of even more effective compounds for the treatment of alcohol dependence. Thus, the specific aims of the project are to: 1) determine the dose-relationship of acute effects of topiramate to reduce alcohol effects related to its abuse and addiction potential. We hypothesize that topiramate will reduce alcohol-induced craving, reward, and euphoria; 2) determine whether chronic treatment with an acutely effective dose of topiramate produces substantial reductions in alcohol-related cue-induced craving, thereby decreasing the potential for treatment relapse. We hypothesize that chronic topiramate administration will desensitize (reduce) alcohol craving produced by alcohol-related sensory cues; and 3) determine whether topiramate interactions with and without alcohol are associated with neurocognitive impairment. Clinical studies including ours have suggested that topiramate use may be associated with neurocognitive effects such as loss of concentration and memory impairment. In our own study, these effects were mild and not associated with reduced treatment compliance. Since alcohol's ability to produce neurocognitive impairment may be mediated through similar ionic mechanisms to that of topiramate, the proposed human laboratory setting affords us the unique opportunity to more clearly delineate topiramate's neurocognitive effects in both the presence and absence of alcohol. This study supports NIAAA's goal to develop effective medications for treating alcoholism and to understand the basic underpinnings of the disease.
- Conditions
- Alcoholism
- Being tested
- Topiramate
- Keywords
- alcoholism /alcohol abuse, alcoholism antagonist, anticonvulsant, cognition, neuropharmacology, substance abuse related behavior, craving, euphoria, relapse /recurrence, patient oriented research
- Medical subject headings
- Alcoholism, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TopiramateDrug
Also called Topamax
200mg twice a day
| Study group | Role | What they receive |
|---|---|---|
| Topiramate | Experimental | Not described Receives: Drug: Topiramate |
| Placebo | Placebo comparator | Not described Receives: Drug: Topiramate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reduction of alcohol-induced craving,reward,and euphoria
Measured: During testing days
Secondary outcomes (2)
Reductions in alcohol-related cue-induced associated with relapse
Measured: During testing days
Determine whether topiramate interactions with and without alcohol are associated with neurocognitive impairment
Measured: During testing days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2005 (estimated)
- Study startSep 2005
- Primary completionJul 2008
- Study completionJul 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AlcoholismStudies of the same condition, open and under way.
- 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bankole Johnson
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health (NIH)
- Responsible party
- Sponsor-investigator, Bankole Johnson, University of Virginia
- Investigators
- Bankole A Johnson, DSc,MD,PhD, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00223639
- Sponsor's protocol ID
- 5R01AA014628-02
- Other IDs
- 5R01AA014628-02
- Status last verified
- Feb 2012
- First submitted
- 19 Sep 2005
- Last updated
- 7 Feb 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- New Medications to Treat Alcohol Dependence
- ClinicalTrials.gov ID
- NCT00223639
- Acronym / sponsor ID
- 5R01AA014628-02
- Conditions
- Alcoholism
- Keywords
- alcoholism /alcohol abuse, alcoholism antagonist, anticonvulsant, cognition, neuropharmacology, substance abuse related behavior, craving, euphoria
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Bankole JohnsonUniversity, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health (NIH)
- Study start
- Sep 2005
- Primary completion
- Jul 2008 (actual)
- Study completion
- Jul 2008 (actual)
- First posted
- 22 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In the last decade, there has been an explosion of new knowledge of the neuroscientific basis of alcohol-seeking behavior. Briefly, medications that modulate mesolimbic dopamine pathways by facilitating gamma amino butyric function and inhibiting the action of excitatory amino acids should reliably diminish alcohol's rewarding effects. Topiramate (a sulfamate-substituted fructo-pyranose derivative) has these characteristics. In support of this concept, we have shown in a phase-II-type medications clinical trial that topiramate is significantly superior to placebo at improving drinking outcomes and decreasing craving among (N = 150) alcohol-dependent individuals. Using the carefully controlled environment of the human laboratory, we are submitting a revised application containing a set of systematic studies to assess directly the mechanistic neuropharmacological processes that are associated with topiramate's anti-drinking effects. This will provide a more comprehensive understanding of the neurobiology of alcohol-seeking behavior and aid in the development of even more effective compounds for the treatment of alcohol dependence. Thus, the specific aims of the project are to: 1) determine the dose-relationship of acute effects of topiramate to reduce alcohol effects related to its abuse and addiction potential. We hypothesize that topiramate will reduce alcohol-induced craving, reward, and euphoria; 2) determine whether chronic treatment with an acutely effective dose of topiramate produces substantial reductions in alcohol-related cue-induced craving, thereby decreasing the potential for treatment relapse. We hypothesize that chronic topiramate administration will desensitize (reduce) alcohol craving produced by alcohol-related sensory cues; and 3) determine whether topiramate interactions with and without alcohol are associated with neurocognitive impairment. Clinical studies including ours have suggested that topiramate use may be associated with neurocognitive effects such as loss of concentration and memory impairment. In our own study, these effects were mild and not associated with reduced treatment compliance. Since alcohol's ability to produce neurocognitive impairment may be mediated through similar ionic mechanisms to that of topiramate, the proposed human laboratory setting affords us the unique opportunity to more clearly delineate topiramate's neurocognitive effects in both the presence and absence of alcohol. This study supports NIAAA's goal to develop effective medications for treating alcoholism and to understand the basic underpinnings of the disease.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Topiramate | Experimental | Drug: Topiramate |
| Placebo | Placebo comparator | Drug: Topiramate |
Who may qualify
- Ages
- 21 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- DSM-IV-R diagnosis of alcohol dependence.
- Drinking on average ≥14 and ≥21 drinks/week in the 30 days prior to enrollment for women and men, respectively, and describing a liking for and frequent use of beer as the alcohol-containing beverage.
- Good physical health as determined by a complete physical examination, electrocardiogram within normal limits, and laboratory screening tests within acceptable range (see exclusion criteria).
- Negative pregnancy test at intake. Women of childbearing potential will be placed on oral contraceptives and also will be expected to use barrier and spermicide as an additional form of contraception if sexually active.
- Literate in English language, and able to read, understand, and complete rating scales and questionnaires accurately.
Key exclusion criteria (28 listed)
- Expression of desire for immediate treatment for alcohol or drug addiction.
- History of mental illness that warrants treatment or would preclude safe participation in the protocol except nicotine dependence, as determined by mental status and psychiatric interview using the Structured Clinical Interview for DSM-IV.
- Acute or chronic organic brain syndrome, schizophrenia, bipolar disorder, or any psychotic disorder.
- Significant medical illness (including hypertension) as determined by history and/or complete physical examination.
- Uncontrolled uterine or cervical bleeding.
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: Topamax200mg twice a day | Drug | Placebo, Topiramate |
Primary outcome
Reduction of alcohol-induced craving,reward,and euphoria
Time frame: During testing days
2 secondary outcomes
Reductions in alcohol-related cue-induced associated with relapse
Time frame: During testing days
Determine whether topiramate interactions with and without alcohol are associated with neurocognitive impairment
Time frame: During testing days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2012.
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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.
Bankole A Johnson, DSc,MD,PhD principal investigator
University of Virginia
2 sites 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 Alcoholism, run by Bankole Johnson at 2 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 7 inclusion and 28 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 7 Feb 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Reduction of alcohol-induced craving,reward,and euphoria (time frame: During testing days). 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 7 Feb 2012.