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
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.