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

Non-alcoholic Fatty Liver Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00677521
• Other study ID #: 1000011557
• Status: Terminated
• Phase: Phase 2
• First received: May 12, 2008
• Last updated: August 16, 2013
• Start date: January 2007
• Est. completion date: August 2008

Study information

• Verified date: August 2013
• Source: The Hospital for Sick Children
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: August 2008
• Est. primary completion date: August 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 10 Years to 18 Years

Eligibility

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 Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Non-alcoholic Fatty Liver Disease

Intervention

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.

Locations

Country	Name	City	State
Canada	The Hospital for Sick Children	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
The Hospital for Sick Children

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improvement of hepatic steatosis as measured by proton magnetic resonance spectroscopy		12 weeks	No
Secondary	Postprandial substrate metabolism reflected in the respiratory quotient (RQ) measured by indirect calorimetry		12 weeks	No