Response of A-T to Metformin and Pioglitazone
Research type
Research Study
Full title
Response of Individuals with Ataxia-Telangiectasia to Metformin and Pioglitazone
IRAS ID
202122
Contact name
Ewan Pearson
Contact email
Sponsor organisation
NHS R&D, TASC
Clinicaltrials.gov Identifier
Duration of Study in the UK
1 years, 9 months, 1 days
Research summary
We hope to study the effects of the diabetes drugs metformin and pioglitazone in the context of Ataxia-Telangiectasia (A-T), to guide clinical management of fatty liver and diabetes in individuals with A-T.
ATM (Ataxia Telangiectasia Mutated) is a gene involved in DNA repair – homozygous recessive mutations cause Ataxia Telangiectasia (A-T), which is associated with - among other things - insulin resistance, “fatty liver” and diabetes.
Metformin is used as first-line medical management of T2DM. Despite this, its mechanism of action is not fully understood. Both tolerance of and response to metformin varies greatly from patient to patient.
A study by our group highlighted ATM as potential genetic link to metformin response. We hope to investigate this potential link by studying non-diabetic A-T patients, using multiple methods including dual-tracer mixed meal studies at three time points: baseline; steady state metformin; and steady state pioglitazone. Other investigations include: MRI to assess fat distribution; blood sampling for biochemical and DNA analysis; and fat biopsy to assess the adipocyte (fat cell) function and response to these drugs.
We are using pioglitazone as a comparator drug. This diabetes drug is known to improve insulin resistance and reduce fat content of the liver. We hope to assess whether metformin or pioglitazone has the greatest impact on the insulin resistance associated with A-T, to enable us to guide clinical management of fatty liver and diabetes in the context of this genetic condition.
In conjunction with the clinical studies we will carry out cell experiments on IPSC-derived hepatocytes from individuals with A-T, to assess drug response at a cellular level. This is a collaboration with another study (“Insignia”), and will not directly involve the individuals we recruit, but may provide further detail of metformin and pioglitazone response in a cell model.
REC name
East of Scotland Research Ethics Service REC 1
REC reference
16/ES/0056
Date of REC Opinion
6 May 2016
REC opinion
Further Information Favourable Opinion