A Pilot Study of Acarbose as Treatment for Pediatric Non-alcoholic Fatty Liver Disease (NAFLD)

This study has been terminated.
(poor recruitment and no student currently interested in working on this project.)
Sponsor:
Information provided by (Responsible Party):
Dr. Paul Pencharz, The Hospital for Sick Children
ClinicalTrials.gov Identifier:
NCT00677521
First received: May 12, 2008
Last updated: August 16, 2013
Last verified: August 2013
  Purpose

The objective of this study is to demonstrate a reduction of intrahepatic fat as measured with Proton Magnetic Resonance Spectroscopy after 12 weeks administration of oral acarbose. The study will also examine the hypothesis of whether the chronic administration of acarbose in patients with NAFLD will influence postprandial substrate metabolism reflected in the RQ measured by indirect calorimetry.


Condition Intervention Phase
Non-alcoholic Fatty Liver Disease
Drug: Acarbose
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of Acarbose as Treatment for Pediatric Non-alcoholic Fatty Liver Disease (NAFLD)

Resource links provided by NLM:


Further study details as provided by The Hospital for Sick Children:

Primary Outcome Measures:
  • Improvement of hepatic steatosis as measured by proton magnetic resonance spectroscopy [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Postprandial substrate metabolism reflected in the respiratory quotient (RQ) measured by indirect calorimetry [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 1
Study Start Date: January 2007
Study Completion Date: August 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: Acarbose
50mg tablet by mouth daily for the first 2 weeks, then twice a day for the next 2 weeks, and then three times a day for the next 8 weeks for a total of 12 weeks.

Detailed Description:

The chronic administration of acarbose has been shown to improve insulin resistance and reverse impaired glucose tolerance. Both these conditions, especially insulin resistance, are physiologically associated with the development and progression of NAFLD. Therefore, we hypothesized that the chronic administration of acarbose attenuates NAFLD by improving glucose handling. This would be reflected in a reduction of intrahepatic fat accumulation. Proton Magnetic Resonance Spectroscopy is a sensitive and non-invasive method to measure changes in intrahepatic fat content. The primary endpoint of this study would be to demonstrate a reduction of intrahepatic fat as measured with Proton Magnetic Resonance Spectroscopy after 12 weeks administration of oral acarbose. Other relevant secondary outcomes that have been previously demonstrated to be associated with improvement of NAFLD included improvement of insulin resistance, normalizing of serum adiponectin, and a lowering of serum Leptin.

A second intent of the study is to test the hypothesis of whether the chronic administration of acarbose in patients with NAFLD will influence postprandial substrate metabolism reflected in the RQ measured by indirect calorimetry. The consequence of insulin resistance is a relative inhibition of fatty oxidation. However, the chronic administration of acarbose improves insulin resistance and dampens the post-prandial surge in serum glucose and insulin. These changes in glucose handling could possibly result in a shift towards a pattern of preferential lipid oxidation. We anticipate either a lowering or blunting of the postprandial RQ after chronic administration of acarbose for 3 months.

  Eligibility

Ages Eligible for Study:   10 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age:10-18 years old
  • Liver biopsy proven NAFLD. NAFLD defined histologically as greater than 5% hepatic macrovesicular steatosis with any degree of chronic inflammation and hepatic fibrosis; clinical definition requires that other liver diseases associated with fatty liver be excluded.
  • Insulin resistance with HOMA-IR score >3.0
  • Hepatic steatosis >5% wet weight on hepatic proton magnetic resonance spectroscopy (1H-MRS)
  • INR <1.2; Conjugated Bilirubin <2umol/L and Albumin >35gm/L

Exclusion Criteria:

  • Type 1 or 2 diabetes mellitus
  • Treatment with oral hypoglycemic agents
  • Ongoing participation in a formal weight loss program or interventional clinical trial
  • Panhypopituitarism and genetic causes of obesity i.e. Prader-Willi syndrome
  • Alcohol consumption >20 g/day
  • Serum creatinine above normal range for age
  • History of previous or predisposition to intestinal obstruction
  • Pre-existing gastrointestinal disease i.e. inflammatory bowel disease; celiac disease
  • Drugs that influence energy metabolism, intestinal transit, substrate metabolism
  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: NCT00677521

Locations
Canada, Ontario
The Hospital for Sick Children
Toronto, Ontario, Canada
Sponsors and Collaborators
The Hospital for Sick Children
Investigators
Principal Investigator: Paul B. Pencharz, MD The Hospital for Sick Children
  More Information

No publications provided

Responsible Party: Dr. Paul Pencharz, Emeritus Scientist, The Hospital for Sick Children
ClinicalTrials.gov Identifier: NCT00677521     History of Changes
Other Study ID Numbers: 1000011557
Study First Received: May 12, 2008
Last Updated: August 16, 2013
Health Authority: Canada: Health Canada

Additional relevant MeSH terms:
Fatty Liver
Liver Diseases
Digestive System Diseases
Acarbose
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Hypoglycemic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 22, 2014