Response of Individuals With Ataxia-Telangiectasia to Metformin and Pioglitazone

• Status: Completed
• Trial end date: 2017-08-30
• Target enrollment: 0
• Participant gender: All

Summary

This study aims to investigate the link between the Ataxia Telangiectasia Mutated (ATM) gene and metformin response. This link has been identified from large studies of the human genome, and this study aims to confirm this link in a clinical study. The ATM gene is involved in DNA repair - if a person inherits a "faulty" copy of this gene from both their parents, they have a genetic condition called Ataxia-telangiectasia (A-T).

A-T is associated with, among other things, a resistance to insulin, which causes fatty liver and diabetes. This study will recruit people who have A-T, but have not developed diabetes, and compare this group to "healthy" controls, i.e. people who do not have A-T or diabetes. The study will compare how the groups respond to two drugs used to treat diabetes (metformin and pioglitazone), with the intention that this will guide the management of diabetes in A-T.

This is an, open label unblinded study recruiting 15 people with A-T and 15 age and gender matched controls. Each participant will have three study visits to the Clinical Research Centre at Ninewells hospital in Dundee - one at baseline, a second after 8 weeks of metformin and the final visit after eight weeks of pioglitazone. During each visit we will carry out a number of investigations to study the insulin resistance of A-T and how it responds to metformin and pioglitazone.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: NHS Tayside
• Collaborator: University of Dundee
• Treatments: Metformin; Pioglitazone

Criteria

Inclusion Criteria:

• Age 18 - 30

• White European descent

• Non-diabetic

• No history of malignancy

• Normal renal function (eGFR > 60 ml/min/1.73m2)

• CASES - Diagnosis of 'classic' Ataxia Telangiectasia (as opposed to 'mild-variant', or related conditions e.g. AOA1)

• CONTROLS - Sex matched to cases

• CONTROLS - BMI 20-25

Exclusion Criteria:

• HbA1c ≥ 48mmol/mol.

• Age out-with 18 - 30

• CASES - Unconfirmed diagnosis of A-T, or non-'classic' form of A-T

• History of diabetes

• History of renal dysfunction

• History of malignancy

• History of heart failure

• Long-term steroid treatment

• Chronic lung infections / bronchiectasis

• Recent (<30 days since completion) or current participation in another clinical trial or interventional study

• Pregnancy

• Athletes (as muscles mass has a direct effect on insulin sensitivity)