AlcoholismPhase 1NCT01113164
Matching Genotypes and Serotonergic Medications for Alcoholism
A Phase 1 study testing Ondansetron and Sertraline in people with Alcoholism, run by Brown University at 1 site in United States.
Trial summary
Sertraline, a serotonin-specific reuptake inhibitor (SSRI) that increases basal serotonin levels, was shown to reduce alcohol consumption in lower risk/severity and later onset (LOA) but not higher risk/severity earlier onset alcoholic individuals (EOA). Read more about this study
- Who is it for?
- Ages 21 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Alcoholism
- What is being tested?
- Ondansetron and Sertraline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 79 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2008to Feb 2012
- Phase
- Phase 1
- 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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Must be between 21 and 65 years old (inclusive).
- Participants may be male or female and must be in good health as confirmed by medical history, baseline physical examination, ECG, laboratory tests, urinalysis and vital signs.
- Female participants must be:
- Postmenopausal for at least one year, surgically sterile, or Practicing an effective method of birth control before entry and throughout the study; have a negative urine pregnancy test at baseline screening and prior to the alcohol challenge sessions.
- Participants must understand that this is not a treatment study.
- A diagnosis of Alcohol dependence using Module E of the structured clinical interview for the DSM-IV (SCID). Alcohol dependent as defined by an AUDIT score ≥ 12 and men must consume ≥ 35 and women ≥ 28 standardized alcoholic beverages a week.
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- Participants must be willing to take oral medication, adhere to the medication regimen and be willing to return for weekly visits and the alcohol challenge sessions.
- Participants must be able to read and comprehend written instructions and comprehend and complete all scale and inventories required by the protocol.
- Participants must have signed an informed consent indicating they understand the purpose of and procedures required for the study and willingness to participate.
Who cannot join
- Pregnancy or breast feeding women.
- Positive urine drug screen at baseline for any illegal substance other than marijuana.
- Participants will be excluded if they have: (a) clinically significant medical abnormalities (i.e. ECG, hematological assessment, bilirubin > 150% of the upper limit of normal or ALT or AST elevations >300% the upper limit of normal, biochemistry including urinalysis, electrolytes,). (Persons with medical conditions that are adequately controlled by their primary care physician will not be excluded.)
- Current use of psychotropic medications that cannot be discontinued
- Medical contraindications for use of sertraline or ondansetron
- Taking drugs that interfere with the metabolism of either drug that cannot be stopped per study physician.
Show all 13Show fewer
- Allergic to sertraline or ondansetron
- Must have a breath alcohol concentration (BrAC) = 0.000 at the beginning of the alcohol challenge sessions.
- Creatinine clearance ≤ 60 dl/min.
- Individuals with a reasonable expectation of being institutionalized during the course of the trial or pending legal charges.
- Participants who have significant alcohol withdrawal symptoms (clinical institute withdrawal assessment for alcohol revised (CIWA-Ar) >10.
- lifetime depression or a history of suicide
- history of seizures (e.g. epilepsy) or migraine headaches -
Trial locations and contacts
1 site in 1 country.
United States1 site
Center for Alcohol and Addiction Studies
Providence, Rhode Island, 02912
About this study
Sertraline, a serotonin-specific reuptake inhibitor (SSRI) that increases basal serotonin levels, was shown to reduce alcohol consumption in lower risk/severity and later onset (LOA) but not higher risk/severity earlier onset alcoholic individuals (EOA). By contrast, ondansetron, a 5-HT3 receptor reduced alcohol consumption in EOAs but not LOAs. To explain this contrast in clinical efficacy, one approach suggests that differential serotonergic response is based on a functional polymorphism of the 5-HTTLPR promoter region of the serotonin re-uptake transporter (SERT). These alleles have typically been classified as biallelic genotypes: LL, SS and SL. The LL variant is postulated to be associated with EOA and the SS/SL variants associated with LOA. To test this hypothesis the investigators therefore propose to match and mismatch serotonergic treatments to genetic polymorphic variants [in 132 non-treatment seeking alcohol dependent volunteers] in a double-blind placebo controlled 2 x 2 design human laboratory study. The investigators propose to randomize non-treatment-seeking alcohol dependent persons based on their 5'-HTTLPR variant genotype (LL or SS/SL) into one of two counterbalanced arms: participants in the first arm (LL) will first receive one drug (either 200mg/day of sertraline or ondansetron 0.5mg/day) for three weeks followed by an alcohol self-administration experiment (ASAE), [with a 1 week down-titration period if sertraline received first, during the first week of the "placebo period"] then receive placebo for two more weeks (this will be a single-blind portion to use as a comparison group and to wash out the pharmacodynamic effects of the first drug) followed by a second ASAE. Participants will then receive the second drug for three weeks followed by a third ASAE [all will receive medication for an additional 1 week period and those receiving sertraline last will be down-titrated]. Participants in the second arm (SS/SL) will receive the same medications in the same balanced design. Individuals in both arms will receive weekly medication management to enhance medication adherence. The long-term objective of this research is to prospectively examine serotonergic treatment matching for alcohol dependence based on genotyping. Of equal importance, the investigators also recognize the strong contribution of additional genetic and environmental influences on alcohol consumption.
Read the detailed description
Medications and genetics have been identified as research priorities by NIAAA. The present application proposes to test two genetic-drug matching hypotheses to better understand heterogeneity among alcoholics. Previous basic science, treatment and genetic research suggests that active drinkers with the LL genetic variant of the serotonin transporter 5'-HTTLPR (a hypothesized genetic risk factor for early onset alcoholism) will respond better to ondansetron than sertraline or placebo. Conversely, active drinkers with the SS or SL genetic variant of the serotonin transporter 5'-HTTLPR (a hypothesized genetic risk factor for late onset alcoholism) will respond better to sertraline than ondansetron or placebo. The objective of this research is to match and mismatch serotonergic treatments to genetic polymorphic variants in a double-blind placebo controlled 2 x 2 design laboratory study where the 2 arms will be counterbalanced. The specific aims are to investigate: (1) whether LL-carriers receiving ondansetron results in a significant reduction in alcohol consumption during an alcohol self-administration experiment (ASAE) and during the period of treatment; (2) whether SL and SS-carriers receiving sertraline will result in a significant reduction in alcohol consumption during an ASAE and during the period of treatment; (3) examine mechanism of action for craving and subjective effects during the ASAE sessions: (4) whether there is a reduction in alcohol consumption during the ASAEs in the presence of the LG, and LA 5-HTTLPR variants and when LL participants receive ondansetron or when LL participants receive sertraline; (5) if the primary aims are moderated by the presence of the C (-1019) G polymorphism of the 5-HT1A gene promoter. We propose to randomize 132 non-treatment-seeking alcohol dependent participants based on their 5'-HTTLPR variant genotype (LL or SS/SL) into one of two counterbalanced arms: e.g. subjects in the first arm will first receive one drug (either 200mg/day of sertraline or ondansetron 0.5mg/day) for three weeks followed by an ASAE, then receive placebo for three weeks (this will be a single-blind portion to use as a comparison group and to wash out the pharmacodynamic effects of the first drug) followed by a second ASAE. Finally, participants will receive the second drug for three weeks followed by a third ASAE. Volunteers in the second arm will receive the same medications in a counter-balanced fashion. There will be a 1-week down titration after the first and third segments for all subjects. The long-term objective of this proposed research is to examine serotonergic treatment matching for alcohol dependence based on genotyping, and begin to investigate patient variation when matched prospectively with one serotonergic treatment or the other.
- Conditions
- Alcoholism
- Being tested
- Ondansetron and Sertraline
- Keywords
- ondansetron, sertraline, lab studies, alcoholism, alcohol dependence
- Medical subject headings
- Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ondansetron and SertralineDrug
capsule 0.25mg twice a day for 21 days and capsule 100mg twice a day
| Study group | Role | What they receive |
|---|---|---|
| Ondansetron, Placebo, Sertraline | Experimental | LL-carriers receiving ondansetron compared to either placebo or sertraline, will result in a significant reduction in alcohol consumption. Receives: Drug: Ondansetron and Sertraline |
| Sertraline, Placebo, Ondansetron | Experimental | SL and SS-carriers receiving sertraline compared to either placebo or ondansetron, will result in a significant reduction in alcohol consumption. Receives: Drug: Ondansetron and Sertraline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of drinks/day consumed
To evaluate the efficacy of ondansetron for reducing drinking in participants who carry the LL variant of the serotonin transporter gene (5-HTTLPR): We hypothesize that LL-carriers receiving ondansetron compared to either placebo or sertraline, will result in a significant reduction in alcohol consumption.
Measured: 13 weeks
Secondary outcomes (1)
Number of Drinks/Day consumed.
To evaluate the efficacy of sertraline for reducing drinking in participants who carry either the SL or SS variants of the 5-HTTLPR: We hypothesize that SL and SS-carriers receiving sertraline compared to either placebo or ondansetron, will result in a significant reduction in alcohol consumption.
Measured: 13 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2010 (estimated)
- Study startSep 2008
- Primary completionFeb 2012
- Study completionFeb 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for AlcoholismStudies of the same condition, open and under way.
- More trials run by Brown UniversityThe 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 1
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 79 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brown University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Responsible party
- Principal investigator, George Kenna, Brown University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01113164
- Sponsor's protocol ID
- AA016079-01A1
- Status last verified
- Feb 2012
- First submitted
- 27 Apr 2010
- Last updated
- 22 Feb 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Kenna GA, Zywiak WH, McGeary JE, Leggio L, McGeary C, Wang S, Grenga A, Swift RM. A within-group design of nontreatment seeking 5-HTTLPR genotyped alcohol-dependent subjects receiving ondansetron and sertraline. Alcohol Clin Exp Res. 2009 Feb;33(2):315-23. doi: 10.1111/j.1530-0277.2008.00835.x. Epub 2008 Nov 19.
PubMed 19032576Kenna GA, Zywiak WH, Swift RM, McGeary JE, Clifford JS, Shoaff JR, Vuittonet C, Fricchione S, Brickley M, Beaucage K, Haass-Koffler CL, Leggio L. Ondansetron reduces naturalistic drinking in nontreatment-seeking alcohol-dependent individuals with the LL 5'-HTTLPR genotype: a laboratory study. Alcohol Clin Exp Res. 2014 Jun;38(6):1567-74. doi: 10.1111/acer.12410. Epub 2014 Apr 28.
PubMed 24773166
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Matching Genotypes and Serotonergic Medications for Alcoholism
- ClinicalTrials.gov ID
- NCT01113164
- Acronym / sponsor ID
- AA016079-01A1
- Conditions
- Alcoholism
- Keywords
- ondansetron, sertraline, lab studies, alcoholism, alcohol dependence
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 79 participants (actual)
- Lead sponsor
- Brown UniversityUniversity, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Study start
- Sep 2008
- Primary completion
- Feb 2012 (actual)
- Study completion
- Feb 2012 (actual)
- First posted
- 29 Apr 2010 (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.
Sertraline, a serotonin-specific reuptake inhibitor (SSRI) that increases basal serotonin levels, was shown to reduce alcohol consumption in lower risk/severity and later onset (LOA) but not higher risk/severity earlier onset alcoholic individuals (EOA). By contrast, ondansetron, a 5-HT3 receptor reduced alcohol consumption in EOAs but not LOAs. To explain this contrast in clinical efficacy, one approach suggests that differential serotonergic response is based on a functional polymorphism of the 5-HTTLPR promoter region of the serotonin re-uptake transporter (SERT). These alleles have typically been classified as biallelic genotypes: LL, SS and SL. The LL variant is postulated to be associated with EOA and the SS/SL variants associated with LOA. To test this hypothesis the investigators therefore propose to match and mismatch serotonergic treatments to genetic polymorphic variants [in 132 non-treatment seeking alcohol dependent volunteers] in a double-blind placebo controlled 2 x 2 design human laboratory study. The investigators propose to randomize non-treatment-seeking alcohol dependent persons based on their 5'-HTTLPR variant genotype (LL or SS/SL) into one of two counterbalanced arms: participants in the first arm (LL) will first receive one drug (either 200mg/day of sertraline or ondansetron 0.5mg/day) for three weeks followed by an alcohol self-administration experiment (ASAE), [with a 1 week down-titration period if sertraline received first, during the first week of the "placebo period"] then receive placebo for two more weeks (this will be a single-blind portion to use as a comparison group and to wash out the pharmacodynamic effects of the first drug) followed by a second ASAE. Participants will then receive the second drug for three weeks followed by a third ASAE [all will receive medication for an additional 1 week period and those receiving sertraline last will be down-titrated]. Participants in the second arm (SS/SL) will receive the same medications in the same balanced design. Individuals in both arms will receive weekly medication management to enhance medication adherence. The long-term objective of this research is to prospectively examine serotonergic treatment matching for alcohol dependence based on genotyping. Of equal importance, the investigators also recognize the strong contribution of additional genetic and environmental influences on alcohol consumption.
Detailed description
Medications and genetics have been identified as research priorities by NIAAA. The present application proposes to test two genetic-drug matching hypotheses to better understand heterogeneity among alcoholics. Previous basic science, treatment and genetic research suggests that active drinkers with the LL genetic variant of the serotonin transporter 5'-HTTLPR (a hypothesized genetic risk factor for early onset alcoholism) will respond better to ondansetron than sertraline or placebo. Conversely, active drinkers with the SS or SL genetic variant of the serotonin transporter 5'-HTTLPR (a hypothesized genetic risk factor for late onset alcoholism) will respond better to sertraline than ondansetron or placebo. The objective of this research is to match and mismatch serotonergic treatments to genetic polymorphic variants in a double-blind placebo controlled 2 x 2 design laboratory study where the 2 arms will be counterbalanced. The specific aims are to investigate: (1) whether LL-carriers receiving ondansetron results in a significant reduction in alcohol consumption during an alcohol self-administration experiment (ASAE) and during the period of treatment; (2) whether SL and SS-carriers receiving sertraline will result in a significant reduction in alcohol consumption during an ASAE and during the period of treatment; (3) examine mechanism of action for craving and subjective effects during the ASAE sessions: (4) whether there is a reduction in alcohol consumption during the ASAEs in the presence of the LG, and LA 5-HTTLPR variants and when LL participants receive ondansetron or when LL participants receive sertraline; (5) if the primary aims are moderated by the presence of the C (-1019) G polymorphism of the 5-HT1A gene promoter. We propose to randomize 132 non-treatment-seeking alcohol dependent participants based on their 5'-HTTLPR variant genotype (LL or SS/SL) into one of two counterbalanced arms: e.g. subjects in the first arm will first receive one drug (either 200mg/day of sertraline or ondansetron 0.5mg/day) for three weeks followed by an ASAE, then receive placebo for three weeks (this will be a single-blind portion to use as a comparison group and to wash out the pharmacodynamic effects of the first drug) followed by a second ASAE. Finally, participants will receive the second drug for three weeks followed by a third ASAE. Volunteers in the second arm will receive the same medications in a counter-balanced fashion. There will be a 1-week down titration after the first and third segments for all subjects. The long-term objective of this proposed research is to examine serotonergic treatment matching for alcohol dependence based on genotyping, and begin to investigate patient variation when matched prospectively with one serotonergic treatment or the other.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ondansetron, Placebo, Sertraline | Experimental | Drug: Ondansetron and SertralineLL-carriers receiving ondansetron compared to either placebo or sertraline, will result in a significant reduction in alcohol consumption. |
| Sertraline, Placebo, Ondansetron | Experimental | Drug: Ondansetron and SertralineSL and SS-carriers receiving sertraline compared to either placebo or ondansetron, will result in a significant reduction in alcohol consumption. |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Must be between 21 and 65 years old (inclusive).
- Participants may be male or female and must be in good health as confirmed by medical history, baseline physical examination, ECG, laboratory tests, urinalysis and vital signs.
- Female participants must be:
- Postmenopausal for at least one year, surgically sterile, or Practicing an effective method of birth control before entry and throughout the study; have a negative urine pregnancy test at baseline screening and prior to the alcohol challenge sessions.
- Participants must understand that this is not a treatment study.
Key exclusion criteria (13 listed)
- Pregnancy or breast feeding women.
- Positive urine drug screen at baseline for any illegal substance other than marijuana.
- Participants will be excluded if they have: (a) clinically significant medical abnormalities (i.e. ECG, hematological assessment, bilirubin > 150% of the upper limit of normal or ALT or AST elevations >300% the upper limit of normal, biochemistry including urinalysis, electrolytes,). (Persons with medical conditions that are adequately controlled by their primary care physician will not be excluded.)
- Current use of psychotropic medications that cannot be discontinued
- Medical contraindications for use of sertraline or ondansetron
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 |
|---|---|---|
| Ondansetron and Sertralinecapsule 0.25mg twice a day for 21 days and capsule 100mg twice a day | Drug | Ondansetron, Placebo, Sertraline, Sertraline, Placebo, Ondansetron |
Primary outcome
Number of drinks/day consumed
Time frame: 13 weeks
To evaluate the efficacy of ondansetron for reducing drinking in participants who carry the LL variant of the serotonin transporter gene (5-HTTLPR): We hypothesize that LL-carriers receiving ondansetron compared to either placebo or sertraline, will result in a significant reduction in alcohol consumption.
1 secondary outcome
Number of Drinks/Day consumed.
Time frame: 13 weeks
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 22 Feb 2012.
- Background: PubMed 19032576Kenna GA, Zywiak WH, McGeary JE, Leggio L, McGeary C, Wang S, Grenga A, Swift RM. A within-group design of nontreatment seeking 5-HTTLPR genotyped alcohol-dependent subjects receiving ondansetron and sertraline. Alcohol Clin Exp Res. 2009 Feb;33(2):315-23. doi: 10.1111/j.1530-0277.2008.00835.x. Epub 2008 Nov 19.
- Derived from this study: PubMed 24773166Kenna GA, Zywiak WH, Swift RM, McGeary JE, Clifford JS, Shoaff JR, Vuittonet C, Fricchione S, Brickley M, Beaucage K, Haass-Koffler CL, Leggio L. Ondansetron reduces naturalistic drinking in nontreatment-seeking alcohol-dependent individuals with the LL 5'-HTTLPR genotype: a laboratory study. Alcohol Clin Exp Res. 2014 Jun;38(6):1567-74. doi: 10.1111/acer.12410. Epub 2014 Apr 28.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ondansetron and Sertraline in people with Alcoholism, run by Brown University 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 9 inclusion and 13 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 22 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 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Number of drinks/day consumed (time frame: 13 weeks). 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 NCT01113164, 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 22 Feb 2012.