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

May 12, 2008
August 16, 2013
January 2007
August 2008   (final data collection date for primary outcome measure)
Improvement of hepatic steatosis as measured by proton magnetic resonance spectroscopy [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00677521 on ClinicalTrials.gov Archive Site
Postprandial substrate metabolism reflected in the respiratory quotient (RQ) measured by indirect calorimetry [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
A Pilot Study of Acarbose as Treatment for Pediatric Non-alcoholic Fatty Liver Disease (NAFLD)
A Pilot Study of Acarbose as Treatment for Pediatric Non-alcoholic Fatty Liver Disease (NAFLD)

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.

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.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Non-alcoholic Fatty Liver Disease
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.
Experimental: 1
Intervention: Drug: Acarbose
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
1
August 2008
August 2008   (final data collection date for primary outcome measure)

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
Both
10 Years to 18 Years
No
Contact information is only displayed when the study is recruiting subjects
Canada
 
NCT00677521
1000011557
No
Dr. Paul Pencharz, The Hospital for Sick Children
The Hospital for Sick Children
Not Provided
Principal Investigator: Paul B. Pencharz, MD The Hospital for Sick Children
The Hospital for Sick Children
August 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP