Alcoholism,Phase 2NCT01504295
A Novel Pharmacotherapy for Alcoholism and Alcohol Liver Disease
A Phase 2 study testing Metadoxine in people with Alcoholism, and Alcoholic Liver Disease, run by Brown University at 1 site in United States.
Trial summary
It is proposed to test metadoxine (MTDX) that it is hypothesized to be significantly beneficial for the treatment of alcoholism and ALD. Metadoxine is currently approved in Europe for acute and chronic alcohol intoxication but has never been tested in the US. Furthermore, MTDX is used in Europe to treat ALD. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Alcoholism,, Alcoholic Liver Disease
- What is being tested?
- Metadoxine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 38 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2012to Feb 2015
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- age ≥18;
- females must be post-menopausal for ≥1 year, surgically sterile, or practicing a birth control before entry and throughout the study; have a negative urine pregnancy test at screening and before randomization;
- current DSM-IV diagnosis of alcohol use disorder (or if relevant at study start-DSM-V) with current (i.e. past 90 days prior to screening) "at-risk" drinking defined as an average overall consumption of ≥28 drinks/week for men and ≥21 drinks/week for women;
- desire abstinence;
- evidence of alcoholic liver disease (ALD) based on a thorough history, physical examination, and laboratory tests (i.e. the De Ritis ratio of AST:ALT ratio ~2:1), which is characteristic of ALD.
Who cannot join
- lifetime DSM diagnosis of schizophrenia, bipolar disorder, or other psychosis;
- in the investigators' opinion, risk of suicide (e.g. active plan, or recent attempt in last year);
- current DSM-IV diagnosis of dependence on any psychoactive substance other than alcohol and nicotine;
- repeated positive urine screen for any substance other than marijuana;
- history of hospitalization for alcohol intoxication delirium or alcohol withdrawal delirium;
- Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) score >10, at any assessment;
Show all 11Show fewer
- having received a psychological and/or pharmacological treatment for alcohol or having participated in a treatment research study within the past 90 days;
- having participated in any clinical trial with an investigational agent within the past 30 days;
- treatment with levodopa/carbidopa or reported diagnosis of Parkinson's disease;
- AST and/or ALT >10 x upper normal limit; Child-Pugh-Turcotte (CPT) score stage C, model for end-stage liver disease (MELD) score >21 (CPT and MELD scores are assessed by blood tests - e.g. bilirubin, albumin, INR, Cr - and medical history); and/or medical history positive for decompensated liver disease (ascites, encephalopathy, variceal bleeding or hepatorenal syndrome) and/or medical history positive for hepatocellular carcinoma; 11) history of allergy to MTDX or PCA and pyridoxol;
- other serious illnesses, e.g. kidney failure.
Trial locations and contacts
1 site in 1 country.
United States1 site
Brown University Center for Alcohol and Addiction Studies
Providence, Rhode Island, 02912
About this study
It is proposed to test metadoxine (MTDX) that it is hypothesized to be significantly beneficial for the treatment of alcoholism and ALD. Metadoxine is currently approved in Europe for acute and chronic alcohol intoxication but has never been tested in the US. Furthermore, MTDX is used in Europe to treat ALD. Preliminary evidence shows that MTDX reduces alcohol consumption in AD individuals. If the role of MTDX in reducing alcohol consumption and improve liver function is confirmed by a rigorous study design, then MTDX might represent a truly innovative pharmacotherapy for AD, given the potential to be used for AD individuals with ALD. However until this proposal, MTDX has never been investigated as a treatment for AD able to reduce both alcohol consumption and improve alcohol-related liver damage via a double-blind placebo-controlled study. This project therefore proposes to conduct a 12-week (followed by a 3-month follow-up), double-blind, placebo-controlled, between-subject randomized clinical trial with MTDX (500mg t.i.d.) in AD individuals.
Read the detailed description
Treatments for ALD have limited success when drinking continues. Cessation of alcohol consumption or a significant reduction in alcohol intake improves histology and survival of patients with any stage of ALD. While alcohol abstinence may not be sufficient to provide a total recovery of ALD, patients with uncomplicated ALD have a 5-year survival of almost 90% if they stop drinking. Consequently, abstinence is the most important therapeutic intervention for patients with ALD. When combined with psychosocial treatments, currently approved medications can improve outcomes for some AD individuals; however, these treatments are unsuccessful for many others. One of the limiting factors that must be taken into consideration when using currently approved medications such as disulfiram or naltrexone is liver function. Given their hepatic metabolism, disulfiram or naltrexone both increase the risk of hepatotoxicity in AD individuals. Therefore, a pharmacotherapy that is effective for AD, that is safe for the liver and able to recover alcohol-related liver damage thereby improving liver function, would be an ideal medication. However as of now, no drug has been found to provide all of these benefits to AD individuals. It is proposed therefore to test metadoxine (MTDX) that it is hypothesized is significantly beneficial for the treatment of alcoholism and ALD. Metadoxine is currently approved in Europe for acute and chronic alcohol intoxication but has never been tested in the US. Furthermore, MTDX is used in Europe to treat ALD. Preliminary evidence shows that MTDX reduces alcohol consumption in AD individuals. If the role of MTDX in reducing alcohol consumption and improve liver function is confirmed by a rigorous study design, then MTDX might represent a truly innovative pharmacotherapy for AD, given the potential to be used for AD individuals with ALD. However until this proposal, MTDX has never been investigated as a treatment for AD able to reduce both alcohol consumption and improve alcohol-related liver damage via a double-blind placebo-controlled study. This project therefore proposes to conduct a 12-week (followed by a 3-month follow-up), double-blind, placebo-controlled, between-subject randomized clinical trial with MTDX (500mg t.i.d.) in AD individuals.
- Conditions
- Alcoholism,, Alcoholic Liver Disease
- Being tested
- Metadoxine
- Medical subject headings
- Alcoholism, Liver Diseases, Alcoholic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetadoxineDrug
Improve Liver Function and Reduce ALcohol Use
| Study group | Role | What they receive |
|---|---|---|
| Metadoxine | Experimental | Metadoxine 500mg tablet t.i.d.for 12 weeks Receives: Drug: Metadoxine |
| Sugar pill | Placebo comparator | Placebo group Receives: Drug: Metadoxine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Days Abstinent (PDA)
We hypothesize that metadoxine (MTDX), compared to placebo significantly increases percent days abstinent (PDA) during the 12 weeks of drug administration, as measured by the timeline follow-back (TLFB).
Measured: 12 weeks
Secondary outcomes (2)
Follow-up PDA
We hypothesize that MTDX, compared to placebo results in significantly higher PDA from discontinuation of the medication to the 3-month follow-up, as measured by the TLFB.
Measured: 12 weeks
Adverse Events
We hypothesize that MTDX, compared to placebo has no greater frequency and intensity of Adverse Events (AE).
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2012 (estimated)
- Study startApr 2012
- Primary completionJan 2015
- Study completionFeb 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Alcoholism,Studies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 38 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
- Investigators
- George A Kenna, PhD RPh, Principal investigator, Brown University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01504295
- Sponsor's protocol ID
- AA021128
- Other IDs
- R21AA021128
- Status last verified
- Jul 2015
- First submitted
- 4 Jan 2012
- Last updated
- 22 Jul 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Shpilenya LS, Muzychenko AP, Gasbarrini G, Addolorato G. Metadoxine in acute alcohol intoxication: a double-blind, randomized, placebo-controlled study. Alcohol Clin Exp Res. 2002 Mar;26(3):340-6.
PubMed 11923586Addolorato G, Ancona C, Capristo E, Gasbarrini G. Metadoxine in the treatment of acute and chronic alcoholism: a review. Int J Immunopathol Pharmacol. 2003 Sep-Dec;16(3):207-14. doi: 10.1177/039463200301600304.
PubMed 14611722Leggio L, Kenna GA, Ferrulli A, Zywiak WH, Caputo F, Swift RM, Addolorato G. Preliminary findings on the use of metadoxine for the treatment of alcohol dependence and alcoholic liver disease. Hum Psychopharmacol. 2011 Dec;26(8):554-9. doi: 10.1002/hup.1244. Epub 2011 Nov 16.
PubMed 22095793Guerrini I, Gentili C, Nelli G, Guazzelli M. A follow up study on the efficacy of metadoxine in the treatment of alcohol dependence. Subst Abuse Treat Prev Policy. 2006 Dec 18;1:35. doi: 10.1186/1747-597X-1-35.
PubMed 17176456Caballeria J, Pares A, Bru C, Mercader J, Garcia Plaza A, Caballeria L, Clemente G, Rodrigo L, Rodes J. Metadoxine accelerates fatty liver recovery in alcoholic patients: results of a randomized double-blind, placebo-control trial. Spanish Group for the Study of Alcoholic Fatty Liver. J Hepatol. 1998 Jan;28(1):54-60. doi: 10.1016/s0168-8278(98)80202-x.
PubMed 9537864
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Novel Pharmacotherapy for Alcoholism and Alcohol Liver Disease
- ClinicalTrials.gov ID
- NCT01504295
- Acronym / sponsor ID
- AA021128
- Conditions
- Alcoholism,, Alcoholic Liver Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Brown UniversityUniversity, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Study start
- Apr 2012
- Primary completion
- Jan 2015 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 5 Jan 2012 (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.
It is proposed to test metadoxine (MTDX) that it is hypothesized to be significantly beneficial for the treatment of alcoholism and ALD. Metadoxine is currently approved in Europe for acute and chronic alcohol intoxication but has never been tested in the US. Furthermore, MTDX is used in Europe to treat ALD. Preliminary evidence shows that MTDX reduces alcohol consumption in AD individuals. If the role of MTDX in reducing alcohol consumption and improve liver function is confirmed by a rigorous study design, then MTDX might represent a truly innovative pharmacotherapy for AD, given the potential to be used for AD individuals with ALD. However until this proposal, MTDX has never been investigated as a treatment for AD able to reduce both alcohol consumption and improve alcohol-related liver damage via a double-blind placebo-controlled study. This project therefore proposes to conduct a 12-week (followed by a 3-month follow-up), double-blind, placebo-controlled, between-subject randomized clinical trial with MTDX (500mg t.i.d.) in AD individuals.
Detailed description
Treatments for ALD have limited success when drinking continues. Cessation of alcohol consumption or a significant reduction in alcohol intake improves histology and survival of patients with any stage of ALD. While alcohol abstinence may not be sufficient to provide a total recovery of ALD, patients with uncomplicated ALD have a 5-year survival of almost 90% if they stop drinking. Consequently, abstinence is the most important therapeutic intervention for patients with ALD. When combined with psychosocial treatments, currently approved medications can improve outcomes for some AD individuals; however, these treatments are unsuccessful for many others. One of the limiting factors that must be taken into consideration when using currently approved medications such as disulfiram or naltrexone is liver function. Given their hepatic metabolism, disulfiram or naltrexone both increase the risk of hepatotoxicity in AD individuals. Therefore, a pharmacotherapy that is effective for AD, that is safe for the liver and able to recover alcohol-related liver damage thereby improving liver function, would be an ideal medication. However as of now, no drug has been found to provide all of these benefits to AD individuals. It is proposed therefore to test metadoxine (MTDX) that it is hypothesized is significantly beneficial for the treatment of alcoholism and ALD. Metadoxine is currently approved in Europe for acute and chronic alcohol intoxication but has never been tested in the US. Furthermore, MTDX is used in Europe to treat ALD. Preliminary evidence shows that MTDX reduces alcohol consumption in AD individuals. If the role of MTDX in reducing alcohol consumption and improve liver function is confirmed by a rigorous study design, then MTDX might represent a truly innovative pharmacotherapy for AD, given the potential to be used for AD individuals with ALD. However until this proposal, MTDX has never been investigated as a treatment for AD able to reduce both alcohol consumption and improve alcohol-related liver damage via a double-blind placebo-controlled study. This project therefore proposes to conduct a 12-week (followed by a 3-month follow-up), double-blind, placebo-controlled, between-subject randomized clinical trial with MTDX (500mg t.i.d.) in AD individuals.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metadoxine | Experimental | Drug: MetadoxineMetadoxine 500mg tablet t.i.d.for 12 weeks |
| Sugar pill | Placebo comparator | Drug: MetadoxinePlacebo group |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- age ≥18;
- females must be post-menopausal for ≥1 year, surgically sterile, or practicing a birth control before entry and throughout the study; have a negative urine pregnancy test at screening and before randomization;
- current DSM-IV diagnosis of alcohol use disorder (or if relevant at study start-DSM-V) with current (i.e. past 90 days prior to screening) "at-risk" drinking defined as an average overall consumption of ≥28 drinks/week for men and ≥21 drinks/week for women;
- desire abstinence;
- evidence of alcoholic liver disease (ALD) based on a thorough history, physical examination, and laboratory tests (i.e. the De Ritis ratio of AST:ALT ratio ~2:1), which is characteristic of ALD.
Key exclusion criteria (11 listed)
- lifetime DSM diagnosis of schizophrenia, bipolar disorder, or other psychosis;
- in the investigators' opinion, risk of suicide (e.g. active plan, or recent attempt in last year);
- current DSM-IV diagnosis of dependence on any psychoactive substance other than alcohol and nicotine;
- repeated positive urine screen for any substance other than marijuana;
- history of hospitalization for alcohol intoxication delirium or alcohol withdrawal delirium;
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 |
|---|---|---|
| MetadoxineImprove Liver Function and Reduce ALcohol Use | Drug | Metadoxine, Sugar pill |
Primary outcome
Percent Days Abstinent (PDA)
Time frame: 12 weeks
We hypothesize that metadoxine (MTDX), compared to placebo significantly increases percent days abstinent (PDA) during the 12 weeks of drug administration, as measured by the timeline follow-back (TLFB).
2 secondary outcomes
Follow-up PDA
Time frame: 12 weeks
Adverse Events
Time frame: 12 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 Jul 2015.
- Background: PubMed 11923586Shpilenya LS, Muzychenko AP, Gasbarrini G, Addolorato G. Metadoxine in acute alcohol intoxication: a double-blind, randomized, placebo-controlled study. Alcohol Clin Exp Res. 2002 Mar;26(3):340-6.
- Background: PubMed 14611722Addolorato G, Ancona C, Capristo E, Gasbarrini G. Metadoxine in the treatment of acute and chronic alcoholism: a review. Int J Immunopathol Pharmacol. 2003 Sep-Dec;16(3):207-14. doi: 10.1177/039463200301600304.
- Background: PubMed 22095793Leggio L, Kenna GA, Ferrulli A, Zywiak WH, Caputo F, Swift RM, Addolorato G. Preliminary findings on the use of metadoxine for the treatment of alcohol dependence and alcoholic liver disease. Hum Psychopharmacol. 2011 Dec;26(8):554-9. doi: 10.1002/hup.1244. Epub 2011 Nov 16.
- Background: PubMed 17176456Guerrini I, Gentili C, Nelli G, Guazzelli M. A follow up study on the efficacy of metadoxine in the treatment of alcohol dependence. Subst Abuse Treat Prev Policy. 2006 Dec 18;1:35. doi: 10.1186/1747-597X-1-35.
- Background: PubMed 9537864Caballeria J, Pares A, Bru C, Mercader J, Garcia Plaza A, Caballeria L, Clemente G, Rodrigo L, Rodes J. Metadoxine accelerates fatty liver recovery in alcoholic patients: results of a randomized double-blind, placebo-control trial. Spanish Group for the Study of Alcoholic Fatty Liver. J Hepatol. 1998 Jan;28(1):54-60. doi: 10.1016/s0168-8278(98)80202-x.
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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.
George A Kenna, PhD RPh principal investigator
Brown University
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 Metadoxine in people with Alcoholism, and Alcoholic Liver Disease, 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 5 inclusion and 11 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 Jul 2015. 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?
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?
Percent Days Abstinent (PDA) (time frame: 12 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 NCT01504295, which also lists 5 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 Jul 2015.