The Effect of Protandim on Non-alcoholic Steatohepatitis (NASH)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT00977730
First received: September 14, 2009
Last updated: February 1, 2013
Last verified: September 2009
  Purpose

The purpose of this study is to evaluate the effect of Protandim on the degree of liver injury after one year of supplementation. Protandim is a nutritional supplement composed of the following 5 botanical extracts: Bacopa Moniera extract, Milk Thistle extract, Ashwagandha powder, Green tea, and Turmeric extract. Protandim is commercially available and can be purchased without a prescription. Our findings could lead to a better understanding of the role of oxidative stress and antioxidant therapy in NASH and may ultimately help improve patient care.

Hypothesis #1: Protandim will lead to a significant improvement in NAS compared to placebo.

Hypothesis #2: Protandim will lead to a significant decrease in serum markers of oxidative stress and liver chemistry tests.

Hypothesis #3: Protandim will lead to decreased levels of TNF- α compared to placebo.


Condition Intervention
Non-Alcoholic Steatohepatitis
Dietary Supplement: Protandim
Dietary Supplement: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effect of the Dietary Supplement Protandim on Non-Alcoholic Steatohepatitis: A Randomized, Double Blind, Placebo-Controlled Study

Resource links provided by NLM:


Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • Change in NAS at study completion in the Protandim group compared to the placebo group. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Enrollment: 70
Study Start Date: July 2008
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Protandim Dietary Supplement: Protandim
1 675 mg capsule Protandim PO/day vs. 1 sugar pill PO/day
Placebo Comparator: Sugar pill Dietary Supplement: Placebo
1 675 mg capsule Protandim PO/day vs. 1 sugar pill PO/day

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age at entry at least 18 years.
  • Serum alanine (ALT) aminotransferase activity that is above the upper limits of normal.
  • Evidence of steatohepatitis on liver biopsy performed within the previous 6 months with a NAFLD activity score (NAS) of at least 3 (of a total possible score of 8) including a score of at least 1 each for steatosis, hepatocellular injury and parenchymal inflammation. Histological criteria of steatohepatitis include: (1) macrovesicular steatosis, (2) acinar zone 3 hepatocellular injury (ballooning degeneration), (3) parenchymal inflammation, and (4) portal inflammation. Additional (but not required) features include the presence of (5) Mallory's hyaline and (6) pericellular and/or sinusoidal fibrosis that predominantly involves zone 3.
  • Written informed consent.
  • Willingness to have a repeat percutaneous liver biopsy following 1 year of supplementation.

Exclusion Criteria:

  • Evidence of another form of liver disease as evidenced by any of the following:

    1. Hepatitis B, as defined by the presence of hepatitis B surface antigen (HBsAg).
    2. Hepatitis C, as defined by the presence of hepatitis C virus (HCV) antibody or HCV RNA in serum.
    3. Autoimmune hepatitis, as defined by anti-nuclear antibody (ANA) of 1:160 or greater (or positive smooth muscle antibody) and liver histology consistent with autoimmune hepatitis or previous response to immunosuppressive therapy.
    4. Autoimmune cholestatic liver disorders, as defined by elevation of anti-mitochondrial antibody of greater than 1:80 (or positive AMA by lab report if a titer is not given) or liver histology consistent with primary biliary cirrhosis or primary (or secondary) sclerosing cholangitis.
    5. Wilson's disease, as defined by ceruloplasmin below the limits of normal and liver histology consistent with Wilson's disease.
    6. Alpha-1-antitrypsin deficiency, as defined by alpha-1-antitrypsin level less than normal and liver histology consistent with alpha-1-antitrypsin deficiency.
    7. Iron overload/hemochromatosis, as defined by the following: elevated transferrin saturation (greater than 45 percent) OR serum ferritin (> 300 microg/L in men or >200 microg/L in women), with one of the following: 1) presence of 3+ or 4+ stainable iron on liver biopsy (if obtained); or 2) Hemochromatosis gene testing showing homozygosity for C282Y or compound heterozygosity for C282Y/H63D (if obtained).
    8. Drug-induced liver disease, as defined on the basis of typical exposure and history.
    9. Intrahepatic and/or extrahepatic duct obstruction, as shown by imaging studies (if obtained).
  • History of excess alcohol ingestion, averaging more than 40 gm/day (3 drinks per day) at any time in the previous 10 years, or history of alcohol intake averaging greater than 40 gm/week (3 drinks/week) in the previous year.
  • Contraindications to liver biopsy: platelet counts less than 75,000/mm(3) or INR>1.4.
  • Stage III or IV fibrosis on baseline liver biopsy.
  • History of gastrointestinal bypass surgery or ingestion of drugs known to produce hepatic steatosis including (but not limited to) corticosteroids, high-dose estrogens, methotrexate, tetracycline or amiodarone in the previous 6 months.
  • Presence of diabetes mellitus as defined by any of the following: 1) fasting plasma glucose of greater than or equal to 126 mg/dl on 2 separate occasions; or 2) diabetic symptoms with a history of random plasma glucose of greater than or equal to 200 mg/dl.
  • Use of anti-diabetic drugs, including insulin, biguanides, sulfonylureas, weight loss medications (either over the counter or prescription), or thiazolidinediones in the previous 6 months. Use of these medications will also be prohibited for the duration of the study.
  • Use of cholesterol lowering medications, including statins.
  • Significant systemic or major illnesses other than liver disease, including congestive heart failure, coronary artery disease, cerebrovascular disease, pulmonary disease with hypoxia, renal failure, organ transplantation, serious psychiatric disease, HIV, or malignancy that, in the opinion of the investigator would preclude adequate follow up.
  • Active substance abuse, such as alcohol, inhaled or injection drugs within the previous one year.
  • Pregnancy.
  • Evidence of hepatocellular carcinoma: alpha-fetoprotein levels greater than 200 ng/ml and/or liver mass on imaging study that is suggestive of liver cancer.
  • Serum creatinine greater than 1.5 mg/dl in men and greater than 1.3 mg/dl in women.
  • Body habitus or other patient issues that necessitated the original liver biopsy being obtained through radiology (by transjugular approach).
  • Abnormal thyroid function, as indicated by an abnormal screening TSH.
  • Total Bilirubin > 2.0
  • AST or ALT > 3 times the upper limits of normal.
  • Serum Sodium <130
  • Hematocrit < 35
  • Any other condition, which, in the opinion of the investigators would impede competence or compliance or possibly hinder completion of the study.
  • Use of any herbal or non-prescription medications.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00977730

Locations
United States, Colorado
University of Colorado at Denver and Health Sciences Center
Denver, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado, Denver
Investigators
Principal Investigator: Gregory Austin, MD, MPH University of Colorado, Denver
  More Information

No publications provided

Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT00977730     History of Changes
Other Study ID Numbers: 07-0848
Study First Received: September 14, 2009
Last Updated: February 1, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Colorado, Denver:
Hepatitis
Fatty Liver
Non Alcoholic Steatohepatitis
Protandim

Additional relevant MeSH terms:
Fatty Liver
Liver Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on August 21, 2014