NCT00573313

Brief Summary

Prior studies in animal models have established that the pathogenesis of alcoholic liver disease (ALD) is regulated in part by the effects of chronic alcohol abuse on hepatic methionine metabolism. The hypothesis of the clinical study was that provision of the methionine metabolite S-adenosylmethionine (SAM) would correct abnormal hepatic methionine metabolism thereby effectively treating ALD. The two goals of the clinical research were a)to determine the clinical relationship of aberrant hepatic methionine metabolism to ALD by comparisons of patterns of serum methionine metabolites in groups of ALD patients, alcoholics without liver disease, and normal healthy subjects, and b) to determine the treatment effects of SAM on patterns of serum methionine metabolites and on the histopathology and biochemical features of liver injury in ALD patients.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
94

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Sep 2005

Typical duration for phase_3

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2005

Completed
2.3 years until next milestone

First Submitted

Initial submission to the registry

December 12, 2007

Completed
2 days until next milestone

First Posted

Study publicly available on registry

December 14, 2007

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2009

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2009

Completed
3.8 years until next milestone

Results Posted

Study results publicly available

June 10, 2013

Completed
Last Updated

May 30, 2017

Status Verified

May 1, 2017

Enrollment Period

3.8 years

First QC Date

December 12, 2007

Results QC Date

February 6, 2013

Last Update Submit

May 24, 2017

Conditions

Keywords

Alcoholic Liver Disease (ALD)S-adenosylmethionineSAMe

Outcome Measures

Primary Outcomes (1)

  • Changes in Serum AST Levels

    Biochemical values for liver function tests and histopathology scores were obtained at week 0 and 24 of the treatment trial, and changes in each were recorded. Here are reported changes in aspartate transaminase (AST) as representative of all changes. Since only baseline values were obtained in the Healthy and Lifestyle counseling groups, there are no recorded changes in these two groups.

    Week 0 to week 24

Secondary Outcomes (1)

  • Changes in Serum SAM

    September 2005- June 2009

Study Arms (2)

S-adenosylmethionine (SAMe)

EXPERIMENTAL

Alcoholic liver disease patients receiving S-adenosylmethionine (SAMe)at 400 mg capsule three times daily for 24 weeks

Drug: S-adenosylmethionine

Sugar pill

PLACEBO COMPARATOR

ALD subjects receiving Placebo three times daily for 24 weeks.

Drug: Placebo

Interventions

Alcoholic liver disease patients received drug at dose of 400 mg three times daily for 24 weeks.

S-adenosylmethionine (SAMe)

Alcoholic liver disease patients received identical size and shape sugar pill placebo three times daily for 24 weeks.

Sugar pill

Eligibility Criteria

Age21 Years - 65 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • ALD) a history of chronic alcoholism according to established AUDIT and WHO criteria with the presence of clinical and laboratory features of established liver disease. Also, willingness to undergo liver biopsies at start and completion of the study, and to comply with study medication or placebo and required clinic visits and blood sampling.
  • a history of chronic alcoholism without evidence of liver disease;
  • healthy subjects without history of alcoholism or presence of liver disease.

You may not qualify if:

  • viral Hepatitis B or C
  • hemochromatosis
  • Wilson Disease
  • sclerosing cholangitis
  • primary biliary cirrhosis
  • other chronic disease
  • renal insufficiency

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of California, Davis Medical Center

Sacramento, California, 95817, United States

Location

Related Publications (2)

  • Medici V, Peerson JM, Stabler SP, French SW, Gregory JF 3rd, Virata MC, Albanese A, Bowlus CL, Devaraj S, Panacek EA, Rahim N, Richards JR, Rossaro L, Halsted CH. Impaired homocysteine transsulfuration is an indicator of alcoholic liver disease. J Hepatol. 2010 Sep;53(3):551-7. doi: 10.1016/j.jhep.2010.03.029. Epub 2010 May 31.

  • Medici V, Virata MC, Peerson JM, Stabler SP, French SW, Gregory JF 3rd, Albanese A, Bowlus CL, Devaraj S, Panacek EA, Richards JR, Halsted CH. S-adenosyl-L-methionine treatment for alcoholic liver disease: a double-blinded, randomized, placebo-controlled trial. Alcohol Clin Exp Res. 2011 Nov;35(11):1960-5. doi: 10.1111/j.1530-0277.2011.01547.x.

MeSH Terms

Conditions

Liver Diseases, Alcoholic

Interventions

S-Adenosylmethionine

Condition Hierarchy (Ancestors)

Liver DiseasesDigestive System DiseasesAlcohol-Induced DisordersAlcohol-Related DisordersSubstance-Related DisordersChemically-Induced Disorders

Intervention Hierarchy (Ancestors)

MethionineAmino Acids, SulfurSulfur CompoundsOrganic ChemicalsAdenosinePurine NucleosidesPurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsAmino AcidsAmino Acids, Peptides, and ProteinsNucleosidesNucleic Acids, Nucleotides, and NucleosidesRibonucleosides

Limitations and Caveats

Relatively small numbers of subjects analyzed with 13 each completers in the treatment and placebo groups. Within each group, violation of protocal by resumption of alcohol intake accounted for dropouts.

Results Point of Contact

Title
Dr. Charles H. Halsted
Organization
University of California Davis

Study Officials

  • Charles H Halsted, MD

    University of California, Davis

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 12, 2007

First Posted

December 14, 2007

Study Start

September 1, 2005

Primary Completion

June 1, 2009

Study Completion

September 1, 2009

Last Updated

May 30, 2017

Results First Posted

June 10, 2013

Record last verified: 2017-05

Locations