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

The Hospital for Sick Children

Status and phase

Terminated

Phase 2

Conditions

Non-alcoholic Fatty Liver Disease

Treatments

Drug: Acarbose

Study type

Interventional

Funder types

Other

Identifiers

NCT00677521

1000011557

Details and patient eligibility

About

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.

Full 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.

Enrollment

1 patient

Sex

All

Ages

10 to 18 years old

Volunteers

No Healthy Volunteers

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