Autoimmune Diabetes Accelerator Prevention Trial

Summary

The autoimmune diabetes ACCELERATOR PREVENTION TRIAL (adAPT) is based on the accelerator hypothesis. The trial is designed to establish whether metformin, an oral hypoglycaemic agent that is known to reduce insulin demand in type 2 diabetes (T2D), can do the same in children at risk of type 1 diabetes (T1D) and thereby prevent disease.

The first phase of adAPT will screen participants aged 5-16 years (inclusive) for islet-related autoantibodies who are the siblings or offspring of individuals diagnosed with T1D before the age of 25years in Scotland and England.

There are four principle islet-related antibodies associated with T1D. The presence of two or more confers a 40% risk of developing T1D in five years. While the presence of none or one antibody carries a similar risk for developing T1D to the general population (1 in 500 in 5years).

It is anticipated that 5% of those screened will be identified as double-antibody positive, these participants will be invited to join the intervention phase of the study - randomised controlled trial (RCT). Up to 200 eligible subjects could be identified by screening with a minimum of 90 being enrolled into the RCT phase.

adAPT is a proposed three stage project. The current protocol defines the screening phase, Stage 1 and seamless entry into Stage 2. Screening will identify children and young people at high risk of developing T1D and invite them to participate in Stage 1 which will involve a minimum of 4 months treatment with either metformin/placebo, however Stage1 treatment will run seamlessly into Stage 2. Stage 1/2 treatment will last up to 21 months (to accommodate 15months screening, 4 months treatment and 2 months analysis). Post Stage1 analysis/ late Stage 2 participation will last up to 36 months (participants enrolled early into Stage 1 will have the longest intervention).

During the Stage1 participants will be tested on three occasions (baseline, month 1 and month 4) for metabolic response using a 5-point mixed meal tolerance test (MMTT). Testing will continue in Stage 1/2 with 3 visits further visits at months 8, 12, 18. Late Stage 2 visits will occur on months 24, 30 \& 36.

Participants will be invited to continue into Stage 3, taking treatment up to 60 months post analysis of Stage 1 and associated protocol amendment and additional consent.

Conditions

• Prediabetic State

Interventions

DRUG

Metformin Hydrochloride

Liquid formula metformin administered by oral syringe in a dose of 10mg/kg body weight once daily for 2 weeks, then to 10mg/Kg twice daily (maximum 500mg twice daily) for a further two weeks during the first month, increasing to 20mg/kg body weight twice daily (maximum 1000mg twice daily) thereafter.

DRUG

Placebo

Liquid formula of placebo administered by oral syringe in an equivalent volume to a metformin dose of 10mg/kg body weight once daily for 2 weeks, then to 10mg/Kg twice daily (maximum 500mg twice daily) for a further two weeks during the first month, increasing to 20mg/kg body weight twice daily (maximum 1000mg twice daily) thereafter.

Sponsors & Collaborators

• University of Dundee

  collaborator OTHER

• University of Bristol

  collaborator OTHER

• University of Exeter

  lead OTHER

Principal Investigators

• Rob Andrews, Prof · University of Exeter

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

5 Years

Max Age

16 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2016-03-30

Primary Completion

2017-06-30

Completion

2017-12-22

Countries

• United Kingdom

Study Locations