Study to Investigate the Effects of Different Doses of S-adenosyl-L-methionine (SAMe) in Subjects With Nonalcoholic Fatty Liver Disease and Non-treated Matched Healthy Volunteers as Control Group

NCT01754714 | Completed Phase 3 Results DMC

• 2 other identifiers: M13-3972012-000975-18
• Study Type: interventional
• Target: 108
• Locations: 4 countries
• Sites: 32

Brief Summary

Investigation the Effects of Different Doses of SAMe in Subjects with Nonalcoholic Fatty Liver Disease and non-treated matched healthy volunteers as control group

Conditions

Non Alcoholic Fatty Liver Disease

Keywords

Steatohepatitis

Outcome Measures

Primary Outcomes (1)

• Methionine Elimination Half-life Measured in Blood.

  After the methionine load, blood samples will be obtained at 0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours. Plasma will be analyzed for methionine.

  0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*

Secondary Outcomes (18)

• Fasting Methionine Concentration of Average Methionine Concentration Versus Time Curve.

  0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*

• 13 Carbon (Natural, Stable Isotope of Carbon) Methionine Breath Test

  0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*

• Hepatic Panel (Liver Laboratory Parameters)

  change from baseline at 6 weeks

• Metabolic Panel (Metabolic Laboratory Parameters)

  change from baseline at 6 weeks

• The Metabolic Clearance Rate Measured in the Blood.

  0.5, 1, 1.5, 3, 4.5, 6, 7.5 and 9 hours*at Week 7*

Other Outcomes (2)

• Immunological/Anti-oxidant Panel (Immunological and Anti-oxidant Laboratory Parameters)

  change from baseline at 6 weeks

• Fibrosis and Apoptosis Markers (Fibrosis and Apoptosis Laboratory Markers)

  change from baseline at 6 weeks

Study Arms (4)

1000 mg SAMe (S-adenosyl-L-methionine)

EXPERIMENTAL

Drug: SAMe 1000 mg

1500 mg SAMe

EXPERIMENTAL

Drug: SAMe 1500 mg

2000 mg SAMe

EXPERIMENTAL

Drug: SAMe 2000 mg

No treatment

NO INTERVENTION

Interventions

SAMe 1000 mg DRUG

1000 mg dose group: one 500 mg capsule fasting in the morning and one 500 mg capsule before dinner

1000 mg SAMe (S-adenosyl-L-methionine)

SAMe 1500 mg DRUG

1500 mg dose group: two 500 mg capsules fasting in the morning and one 500 mg capsule before dinner

1500 mg SAMe

SAMe 2000 mg DRUG

2000 mg dose group: two 500 mg capsules fasting in the morning and two 500 mg capsules before dinner

2000 mg SAMe

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects with non-alcoholic steatohepatitis based on histology in medical history within the last 3 years
• Subjects in a stable metabolic condition since histology for NASH (Non-alcoholic Steatohepatitis)

You may not qualify if:

• Subjects with extrahepatic biliary obstruction
• Subjects with primary sclerosing cholangitis (PSC)
• Subjects with primary biliary cirrhosis (PBC)
• Any form of malignancy within the past 5 years and/or basal cell carcinoma and squamous cell carcinoma of the skin within the past two years
• History of active substance abuse (oral, inhaled or injected) within one year prior to the study
• Subjects with renal impairment (creatinine level of \>2.0 mg/dL)
• Subjects with a known hypersensitivity to the active substance (ademetionine) or methionine or to any of the inactive ingredients
• Subjects with known genetic defects affecting the methionine cycle and/or causing homocystinuria and/or hyperhomocysteinemia (e.g., cystathionine beta-synthase deficiency, Vitamin B12 metabolism defect)
• Subjects on total parenteral nutrition in the year prior to screening
• Subjects after or planned for bariatric surgery (jejunoileal bypass or gastric weight loss surgery)
• Extrahepatic cholestasis (proven by ultrasound)
• Subjects with alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \> 5 upper limit of normal (ULN)
• Subject with serum total bilirubin (STB) \> 5 ULN
• Subjects after liver transplantation and subjects on the waiting list for liver transplantation
• Subjects with any of the following disease in medical history:

Sponsors & Collaborators

• Abbott: lead
• PPD Development, LP: collaborator

Study Sites (32)

Site Reference ID 93914

Amiens, 80054, France

Location

Site Reference ID 93895

Angers, 49933, France

Location

Site Reference ID 93894

Bobigny, 93009, France

Location

Site Reference ID 93913

Montpellier, 34295, France

Location

Site Reference ID 93916

Nice, 06202, France

Location

Site Reference ID 93915

Paris, 75012, France

Location

Site Reference ID 93893

Paris, 75651, France

Location

Site Reference ID 93896

Pessac, 33604, France

Location

Site Reference ID 93953

Bonn, 53127, Germany

Location

Site Reference ID 93954

Frankfurt, 60594, Germany

Location

Site Reference ID 93935

Freiburg im Breisgau, 79106, Germany

Location

Site Reference ID 93955

Halle, 06120, Germany

Location

Site Reference ID 93917

Hanover, 30625, Germany

Location

Site Reference ID 93933

Homburg, 66424, Germany

Location

Site Reference ID 94015

Leipzig, 04103, Germany

Location

Site Reference ID 93918

Mainz, 55131, Germany

Location

Site Reference ID 94014

Ulm, 89081, Germany

Location

Site reference ID/Investigator # 109455

Bydgoszcz, 85-030, Poland

Location

Site Reference ID 93958

Chorzów, 41-500, Poland

Location

Site Reference ID 93973

Krakow, 31-531, Poland

Location

Site Reference ID 93956

Lodz, 91-347, Poland

Location

Site Reference ID 93957

Mysłowice, 41-400, Poland

Location

Site Reference ID 93974

Warsaw, 02-507, Poland

Location

Site Reference ID 93975

Wroclaw, 50-220, Poland

Location

Site reference ID ORG-000905

Krasnoyarsk, 660022, Russia

Location

Site reference ID ORG-000906

Moscow, 119435, Russia

Location

Site reference ID ORG-000900

Nizhny Novgorod, 603126, Russia

Location

Site reference ID ORG-000907

Novosibirsk, 630084, Russia

Location

Site reference ID ORG-000903

Omsk, 644043, Russia

Location

Site reference ID ORG-000920

Rostov-on-Don, 344022, Russia

Location

Site reference ID ORG-000904

Samara, 443011, Russia

Location

Site reference ID ORG-000901

Stavropol, 355017, Russia

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Fatty Liver

Interventions

S-Adenosylmethionine

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Methionine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Amino Acids; Amino Acids, Peptides, and Proteins; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Associate Director Clinical Services
• Organization: Abbott

taco.baardman@abbott.com

+31 29-44-79-196

Study Officials

• Suntje Sander-Struckmeier, PhD

  Abbott

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2012
• First Posted: December 21, 2012
• Study Start: December 1, 2012
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: February 19, 2016
• Results First Posted: February 19, 2016

Record last verified: 2016-01

Locations

FR (8); DE (9); PL (7); RU (8)