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.

Study Overview

• Status: Terminated
• Conditions: Non-alcoholic Fatty Liver Disease
• Intervention / Treatment: Drug: Acarbose

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.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada
      • The Hospital for Sick Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Improvement of hepatic steatosis as measured by proton magnetic resonance spectroscopy	12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Postprandial substrate metabolism reflected in the respiratory quotient (RQ) measured by indirect calorimetry	12 weeks

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children
• Investigators: Principal Investigator: Paul B. Pencharz, MD, The Hospital for Sick Children

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): August 1, 2008
• Study Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: May 12, 2008
• First Submitted That Met QC Criteria: May 12, 2008
• First Posted (Estimate): May 14, 2008

Study Record Updates

• Last Update Posted (Estimate): August 19, 2013
• Last Update Submitted That Met QC Criteria: August 16, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Glycoside Hydrolase Inhibitors; Acarbose
• Other Study ID Numbers: 1000011557