Prediabetic StatePhase 4adAPTNCT02881528
Autoimmune Diabetes Accelerator Prevention Trial
A Phase 4 study testing Metformin Hydrochloride in people with Prediabetic State, run by University of Exeter at 5 sites in United Kingdom.
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… Read more about this study
- Who is it for?
- Ages 5 to 16 yearsHealthy volunteers can take part
- Conditions the study is for
- Prediabetic State
- What is being tested?
- Metformin Hydrochloride
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 5 sitesUnited Kingdom
- Study dates
- 30 Mar 2016to 22 Dec 2017
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 16 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Aged 5-16years (inclusive) at time of screening
- Offspring of parents or siblings who themselves developed T1D before the age of 25years
- Parent /Participant is willing and able to give informed consent/assent
- Additional Inclusion Criteria for Intervention Phase
- Individuals identified by screening to be sero-positive for at least two of the four islet-related antibodies; Insulin Autoantibodies (IAA), Islet Antigen-2 Autoantibodies (IA-2A), Glutamic Acid Decarboxylase Autoantibodies (GADA), Zinc Transporter 8 Autoantibodies (ZnT8).
Who cannot join
- Parent /Participant is unwilling/unable to give informed consent/assent
- Under 5y or over 17y at time of screening
- Offspring of parents or siblings who themselves developed T1D after the age of 25years
- Known to have physician diagnosed diabetes
- Already taking metformin
- Physically or psychologically unable to participate
Show all 20Show fewer
- Taking medication likely to increase insulin resistance or blood glucose levels (e.g. oral/systemic; steroids, growth hormone, beta-2-agonists, diuretics or angiotensin-converting-enzyme (ACE) -inhibitors.)
- Suffering from anoxia, cardiovascular insufficiency, renal or hepatic disease or sepsis - contraindication to metformin
- Participating in another clinical trial (other than observational trials and registries) concurrently or within 30 days prior to screening for entry into this study
- Additional Exclusion Criteria for Intervention Phase:
- Development of diabetes during the screening phase
- Identified by screening to be sero-negative (fewer than two of the four islet-related antibodies (IAA, GAD, IA-2, ZnT8)
- Fasting Blood Glucose of ≥ 7 mmol/L at Month 0
- Postmenarche female participants of childbearing potential who are pregnant or lactating
- Postmenarche female participants of childbearing potential must be sexually abstinent or use another acceptable form of contraception during study participation
- Renal failure or renal dysfunction (creatinine clearance < 60 mL/min)
- Acute conditions with the potential to alter renal function such as, severe infection, shock
- Acute or chronic disease which may cause tissue hypoxia such as: cardiac or respiratory failure, recent myocardial infarction, shock, hepatic insufficiency acute alcohol intoxication, alcoholism
- Known allergies to milk and/or soya
- Hypersensitivity to metformin hydrochloride or any of the excipients: Parahydroxybenzoates may cause allergic reactions (possibly delayed); Liquid mannitol - patients with rare hereditary fructose intolerance.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United Kingdom5 sites
NHS Grampian
Aberdeen, Grampian, AB25 2ZG
NHS Tayside
Dundee, Tayside, DD1 9SY
NHS Greater Glasgow & Clyde
Glasgow, G3 8SJ
NHS Ayrshire & Arran
Kilmarnock, Ayrshire, KA2 0BE
NHS Lanarkshire
Wishaw, Lanarkshire, ML2 0DP
About this study
Official title: Autoimmune Diabetes Accelerator Prevention Trial - adAPT Stage 1
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.
Read more
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.
Read the detailed description
adAPT is a randomised double-blind placebo-controlled Phase IV clinical trial.
Metformin, a licensed medicine but will be tested out with its current license (off-label). Participants will either receive metformin (liquid) or matched placebo in a double blind manner; neither the participant or study team will know the allocation.
Metformin, the study medication, reduces the demand for insulin in Type 2 diabetes (T2D). adAPT will test if metformin can also reduce insulin demand in children at risk of Type 1 Diabetes (T1D). adAPT has an adaptive design with each stage informing the next with progression depend upon the previous stages outcome Stage 1 exposes each participant to metformin or placebo for four months, following which they seamlessly enter Stage 2. However, because recruitment rolls over 15 months many of those recruited early on will have entered Stage 2 before some even reach Stage 1. Accordingly, the protocol and submission also outlines Stages 2.
A successful Stage 1 will lead-on to a clinical outcome trial (Stages 2 and 3) which, if successful, will fundamentally change our understanding of what causes diabetes and how to prevent it. Stage 1 is required to confirm that adAPT trial design is achievable. Outcome evaluation will be undertaken at 21 months. Stage 2 (proof-of-concept) will test if metformin can slow-down the development of diabetes. The outcome data form Stage 1 will allow for power to be calculated to drive the number of participants required for the study for Stages 2 (and 3). It is proposed that once the power and thus population numbers are established for Stage 2 (out with this protocol) that new participants will enter Stage 1 via screening and follow the established trial pathway.
Diabetes biological markers will be measured and formally assessed at the end of Stage 2, after 36 months. Stage 3 will occur if metformin treatment in Stage 2 is proven to be better than placebo for slowing the development of diabetes. Stage 3 will further investigate the development of diabetes between the groups, using biological markers and clinical outcomes at five years.
Children/adolescents aged between 5-16 years (inclusive) at the time of screening and who are siblings or offspring of people diagnosed with type 1 diabetes before the age of 25 are eligible to be invited to participate in the screening phase of adAPT. Families/ children will be invited to participate in screening and will informed of the study by invitation letter (via the index T1D patient) from their designated clinician/Principal Investigator (PI) or via their family practitioner through Scottish Primary Care Research Network/Clinical Research Network (SPCRN/CRN). In addition potential participants may contact the study team independently (self-referral) in response to media/press and internet coverage. Those invited via letter will be requested to either return the reply slip, or call/Short Message Service (SMS)/email the study team to register their interest.
Parent and child age-appropriate Screening Information will be provided and written consent and assent will be completed. Consent/assent will only occur after a minimum of 24 hours has elapsed from study information provision.
Screening will take place in clinically appropriate locations. Screening requires a small non-fasting blood sample (3.5 mls). Participants will be offered topical anaesthesia prior to the blood sample being taken.
This sample will be tested for four islet-related antibodies. Two or more antibodies will infer a positive test, while one or less will conclude a negative test. It is anticipated that approximately 5% of the screened population will present with a positive results and thus a 40% risk of diabetes over 5 years and thus are eligible to be invited into Stage 1 of the study. It is expected that 95% of people screened will test negative and their participation will conclude (except for remote data linkage relating to diabetes diagnosis for 10 years post study participation). The antibody tests are posted to the study's partner laboratory in Bristol, United Kingdom (UK) with results being available within an 8 week timeframe.
Antibody positive participants/families will receive a result consultation and an invitation to the intervention stage of the study. Age-appropriate information sheets will be provided for children/adolescents in addition to parents/guardian information.
If child/adolescent and parent/guardian assent/consent to participant in the RCT phase the following visits will take place:
Stage 1 Month 0 (M0) visit - lasting approximately 2.5 to 3 hours:
Measure participant height, weight and waist circumference. Urine pregnancy test for all menstruating female participants. Topical anaesthesia will be offered and applied if participant agreeable. (Following assessment of anaesthesia) a cannula will be inserted for blood sampling.
Safety blood samples to measure fasting glucose levels, full blood count, liver function, urea and electrolytes. Samples sent to local National Health Service (NHS) hospital accredited laboratories.
Research blood samples: Antibodies, Immunology, deoxyribonucleic acid (DNA -with consent and Vitamin B12.
Mixed Meal Tolerance Testing (MMTT) baseline samples (Insulin, C-peptide and Glucose) followed by Ensure Plus (or equivalent) drink at 6ml per kg dose (maximum 360ml) with 4 further blood tests being obtained at 30 minute intervals (via the in situ cannula) for 2 hours; Time points: 0, 30, 60, 90, 120 minutes.
Randomisation will occur following eligibility criteria and safety sample results review by PI. If the participant is not eligible the participant and parent will be informed of the rationale for non-eligibility and the participant' s family doctor will be informed of any clinically significant findings (with consent.) Participants will be provided with study medication (Metformin or placebo) and given instructions on dose and administration after randomisation has taken place at M0 visit.
If eligible, more than one sibling can be screened and, if seropositive, recruited. To avoid treatment contamination, immediate family members will be allocated to the same treatment group, with the first family member tested being the one who is randomly allocated.
The required study medication dose is calculated using the participant's weight using a dosing algorithm using 2.5kg increments to the nearest 0.5mls.
On commencement of treatment metformin can cause gastric intolerance, therefore to minimise side effects for the first two weeks participants will be requested to take once daily 10mg/kg - half the target dose. Medication is administered/ taken orally.
Month 0 + 2 weeks:
Research nurse will contact the parent/participant to review tolerability and if tolerated increase to twice daily dosing of 10mg/kg and will assess adverse event profile. New written dosing instructions will be provided. If the participant is not tolerating dose they will be withdrawn from the study.
Month 1 Visit - lasting approximately 2.5 to 3 hours:
Procedures are the same as M0 without an antibody blood sample. Study medication is increased to the target dose of 20mg/kg, twice daily. Participants are provided with new written dosing instructions.
Month 1 + 1 week:
Research nurse will phone the parent/participant to review tolerability of up-titrated dose and assess adverse event profile. If the dose is not tolerated they their dose will be reduced to the previous tolerated dose of 10mg/kg, twice a day which will continue for the remainder of the trial. Where down-titration occurs new written dosing instructions will be provided.
Month 4, 8, 12, 18, (Late Stage 2: 24, 30, 36) - lasting approximately 2.5 to 3 hours:
Procedures are the same as M0 with antibody sample. Clinical significant results will reported as per local laboratory ranges and protocol.
Months 1, 2 \& 3 and every 3 months or as required the research nurse will contact parent/participant to assess adverse event profile.
- Conditions
- Prediabetic State
- Being tested
- Metformin Hydrochloride, Placebo
- Keywords
- Type 1 Diabetes, Juvenile Diabetes
- Medical subject headings
- Prediabetic State, Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metformin HydrochlorideDrug
Also called Metformin
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Metformin Hydrochloride | Experimental | Metformin Hydrochloride Ph Eur oral solution (100mg/1ml) Starting Dose 10mg/Kg body weight once daily for 2 weeks, increasing to 10mg/Kg body weight twice daily if tolerated, increasing to target dose of 20mg/Kg body weight twice daily (max 1000mg twice daily) at Month 1 (4 weeks post randomization).
Down-titration to 10mg/kg twice daily if target dose not tolerated. Stage 1: Dosing for up to 15 months (option to extend to Stage 2: 36 months) Receives: Drug: Metformin Hydrochloride |
| Placebo | Placebo comparator | Placebo (100mg/1ml) Starting Dose 10mg/Kg body weight once daily for 2 weeks, increasing to 10mg/Kg body weight twice daily if tolerated, increasing to target dose of 20mg/Kg body weight twice daily (max 1000mg twice daily) at Month 1 (4 weeks post randomization).
Down-titration to 10mg/kg twice daily if target dose not tolerated. Stage 1: Dosing for up to 15 months (option to extend to Stage 2: 36 months) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Between group difference in reduction of Homeostatic Model Assessment (HOMAR) of Insulin Resistance (IR, mass units).
Note: study not powered to nominate a primary outcome as feasibility study.
Measured: 21 months (Stage1)
Between group difference in reduction in beta cell demand as measured by serum glucose (mmol/L) and C-peptide (ng/mL)
Note: study not powered to nominate a primary outcome as feasibility study.
Measured: 21 months
Secondary outcomes (2)
Feasibility of a randomized controlled trial in children who are at high risk of T1D as measured by recruitment rates (%)
Measured: 21 months
Feasibility of a randomized controlled trial in children who are at high risk of T1D as measured by attrition rates (%)
Measured: 21 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2016 (estimated)
- Study start30 Mar 2016
- Primary completion30 Jun 2017 (estimated)
- Study completion22 Dec 2017
Why it stopped: Poor Recruitment prior to end of funding timelines.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prediabetic StateStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Exeter
- Sponsor type
- University, hospital or other
- Collaborators
- University of Dundee, University of Bristol
- Responsible party
- Sponsor
- Investigators
- Rob Andrews, Prof, Principal investigator, University of Exeter
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02881528
- Sponsor's protocol ID
- 15/135763
- Other IDs
- 2015-000748-41, 15/ES/0075, 2015
- Acronym
- adAPT
- Status last verified
- Oct 2018
- First submitted
- 28 Mar 2016
- Last updated
- 16 Oct 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Autoimmune Diabetes Accelerator Prevention Trial - adAPT Stage 1
- ClinicalTrials.gov ID
- NCT02881528
- Acronym / sponsor ID
- adAPT / 15/135763
- Conditions
- Prediabetic State
- Keywords
- Type 1 Diabetes, Juvenile Diabetes
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Poor Recruitment prior to end of funding timelines.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of ExeterUniversity, hospital or other
- Collaborators
- University of Dundee, University of Bristol
- Study start
- 30 Mar 2016 (actual)
- Primary completion
- 30 Jun 2017 (estimated)
- Study completion
- 22 Dec 2017 (actual)
- First posted
- 29 Aug 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
adAPT is a randomised double-blind placebo-controlled Phase IV clinical trial.
Metformin, a licensed medicine but will be tested out with its current license (off-label). Participants will either receive metformin (liquid) or matched placebo in a double blind manner; neither the participant or study team will know the allocation.
Metformin, the study medication, reduces the demand for insulin in Type 2 diabetes (T2D). adAPT will test if metformin can also reduce insulin demand in children at risk of Type 1 Diabetes (T1D). adAPT has an adaptive design with each stage informing the next with progression depend upon the previous stages outcome Stage 1 exposes each participant to metformin or placebo for four months, following which they seamlessly enter Stage 2. However, because recruitment rolls over 15 months many of those recruited early on will have entered Stage 2 before some even reach Stage 1. Accordingly, the protocol and submission also outlines Stages 2.
A successful Stage 1 will lead-on to a clinical outcome trial (Stages 2 and 3) which, if successful, will fundamentally change our understanding of what causes diabetes and how to prevent it. Stage 1 is required to confirm that adAPT trial design is achievable. Outcome evaluation will be undertaken at 21 months. Stage 2 (proof-of-concept) will test if metformin can slow-down the development of diabetes. The outcome data form Stage 1 will allow for power to be calculated to drive the number of participants required for the study for Stages 2 (and 3). It is proposed that once the power and thus population numbers are established for Stage 2 (out with this protocol) that new participants will enter Stage 1 via screening and follow the established trial pathway.
Diabetes biological markers will be measured and formally assessed at the end of Stage 2, after 36 months. Stage 3 will occur if metformin treatment in Stage 2 is proven to be better than placebo for slowing the development of diabetes. Stage 3 will further investigate the development of diabetes between the groups, using biological markers and clinical outcomes at five years.
Children/adolescents aged between 5-16 years (inclusive) at the time of screening and who are siblings or offspring of people diagnosed with type 1 diabetes before the age of 25 are eligible to be invited to participate in the screening phase of adAPT. Families/ children will be invited to participate in screening and will informed of the study by invitation letter (via the index T1D patient) from their designated clinician/Principal Investigator (PI) or via their family practitioner through Scottish Primary Care Research Network/Clinical Research Network (SPCRN/CRN). In addition potential participants may contact the study team independently (self-referral) in response to media/press and internet coverage. Those invited via letter will be requested to either return the reply slip, or call/Short Message Service (SMS)/email the study team to register their interest.
Parent and child age-appropriate Screening Information will be provided and written consent and assent will be completed. Consent/assent will only occur after a minimum of 24 hours has elapsed from study information provision.
Screening will take place in clinically appropriate locations. Screening requires a small non-fasting blood sample (3.5 mls). Participants will be offered topical anaesthesia prior to the blood sample being taken.
This sample will be tested for four islet-related antibodies. Two or more antibodies will infer a positive test, while one or less will conclude a negative test. It is anticipated that approximately 5% of the screened population will present with a positive results and thus a 40% risk of diabetes over 5 years and thus are eligible to be invited into Stage 1 of the study. It is expected that 95% of people screened will test negative and their participation will conclude (except for remote data linkage relating to diabetes diagnosis for 10 years post study participation). The antibody tests are posted to the study's partner laboratory in Bristol, United Kingdom (UK) with results being available within an 8 week timeframe.
Antibody positive participants/families will receive a result consultation and an invitation to the intervention stage of the study. Age-appropriate information sheets will be provided for children/adolescents in addition to parents/guardian information.
If child/adolescent and parent/guardian assent/consent to participant in the RCT phase the following visits will take place:
Stage 1 Month 0 (M0) visit - lasting approximately 2.5 to 3 hours:
Measure participant height, weight and waist circumference. Urine pregnancy test for all menstruating female participants. Topical anaesthesia will be offered and applied if participant agreeable. (Following assessment of anaesthesia) a cannula will be inserted for blood sampling.
Safety blood samples to measure fasting glucose levels, full blood count, liver function, urea and electrolytes. Samples sent to local National Health Service (NHS) hospital accredited laboratories.
Research blood samples: Antibodies, Immunology, deoxyribonucleic acid (DNA -with consent and Vitamin B12.
Mixed Meal Tolerance Testing (MMTT) baseline samples (Insulin, C-peptide and Glucose) followed by Ensure Plus (or equivalent) drink at 6ml per kg dose (maximum 360ml) with 4 further blood tests being obtained at 30 minute intervals (via the in situ cannula) for 2 hours; Time points: 0, 30, 60, 90, 120 minutes.
Randomisation will occur following eligibility criteria and safety sample results review by PI. If the participant is not eligible the participant and parent will be informed of the rationale for non-eligibility and the participant' s family doctor will be informed of any clinically significant findings (with consent.) Participants will be provided with study medication (Metformin or placebo) and given instructions on dose and administration after randomisation has taken place at M0 visit.
If eligible, more than one sibling can be screened and, if seropositive, recruited. To avoid treatment contamination, immediate family members will be allocated to the same treatment group, with the first family member tested being the one who is randomly allocated.
The required study medication dose is calculated using the participant's weight using a dosing algorithm using 2.5kg increments to the nearest 0.5mls.
On commencement of treatment metformin can cause gastric intolerance, therefore to minimise side effects for the first two weeks participants will be requested to take once daily 10mg/kg - half the target dose. Medication is administered/ taken orally.
Month 0 + 2 weeks:
Research nurse will contact the parent/participant to review tolerability and if tolerated increase to twice daily dosing of 10mg/kg and will assess adverse event profile. New written dosing instructions will be provided. If the participant is not tolerating dose they will be withdrawn from the study.
Month 1 Visit - lasting approximately 2.5 to 3 hours:
Procedures are the same as M0 without an antibody blood sample. Study medication is increased to the target dose of 20mg/kg, twice daily. Participants are provided with new written dosing instructions.
Month 1 + 1 week:
Research nurse will phone the parent/participant to review tolerability of up-titrated dose and assess adverse event profile. If the dose is not tolerated they their dose will be reduced to the previous tolerated dose of 10mg/kg, twice a day which will continue for the remainder of the trial. Where down-titration occurs new written dosing instructions will be provided.
Month 4, 8, 12, 18, (Late Stage 2: 24, 30, 36) - lasting approximately 2.5 to 3 hours:
Procedures are the same as M0 with antibody sample. Clinical significant results will reported as per local laboratory ranges and protocol.
Months 1, 2 \& 3 and every 3 months or as required the research nurse will contact parent/participant to assess adverse event profile.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metformin Hydrochloride | Experimental | Drug: Metformin HydrochlorideMetformin Hydrochloride Ph Eur oral solution (100mg/1ml) Starting Dose 10mg/Kg body weight once daily for 2 weeks, increasing to 10mg/Kg body weight twice daily if tolerated, increasing to target dose of 20mg/Kg body weight twice daily (max 1000mg twice daily) at Month 1 (4 weeks post randomization). Down-titration to 10mg/kg twice daily if target dose not tolerated. Stage 1: Dosing for up to 15 months (option to extend to Stage 2: 36 months) |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo (100mg/1ml) Starting Dose 10mg/Kg body weight once daily for 2 weeks, increasing to 10mg/Kg body weight twice daily if tolerated, increasing to target dose of 20mg/Kg body weight twice daily (max 1000mg twice daily) at Month 1 (4 weeks post randomization). Down-titration to 10mg/kg twice daily if target dose not tolerated. Stage 1: Dosing for up to 15 months (option to extend to Stage 2: 36 months) |
Who may qualify
- Ages
- 5 to 16 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Aged 5-16years (inclusive) at time of screening
- Offspring of parents or siblings who themselves developed T1D before the age of 25years
- Parent /Participant is willing and able to give informed consent/assent
- Additional Inclusion Criteria for Intervention Phase
- Individuals identified by screening to be sero-positive for at least two of the four islet-related antibodies; Insulin Autoantibodies (IAA), Islet Antigen-2 Autoantibodies (IA-2A), Glutamic Acid Decarboxylase Autoantibodies (GADA), Zinc Transporter 8 Autoantibodies (ZnT8).
Key exclusion criteria (20 listed)
- Parent /Participant is unwilling/unable to give informed consent/assent
- Under 5y or over 17y at time of screening
- Offspring of parents or siblings who themselves developed T1D after the age of 25years
- Known to have physician diagnosed diabetes
- Already taking metformin
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Metformin HydrochlorideAlso: MetforminLiquid 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 | Metformin Hydrochloride |
| PlaceboLiquid 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. | Drug | Placebo |
Primary outcome
Between group difference in reduction of Homeostatic Model Assessment (HOMAR) of Insulin Resistance (IR, mass units).
Time frame: 21 months (Stage1)
Note: study not powered to nominate a primary outcome as feasibility study.
Between group difference in reduction in beta cell demand as measured by serum glucose (mmol/L) and C-peptide (ng/mL)
Time frame: 21 months
Note: study not powered to nominate a primary outcome as feasibility study.
2 secondary outcomes
Feasibility of a randomized controlled trial in children who are at high risk of T1D as measured by recruitment rates (%)
Time frame: 21 months
Feasibility of a randomized controlled trial in children who are at high risk of T1D as measured by attrition rates (%)
Time frame: 21 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2018.
- Individual participant dataSharing planned: No
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Prediabetes
Not yet recruitingEarly Phase 1
Efficacy of the pA1c®HI Postbiotic in Metabolic Regulation in Healthy Individuals With Hyperglycemia
Hyperglycemias, Prediabetes
Recruiting
Smartwatch-based Intervention for Cardiovascular Health (SWITCH)
Overweight , Obesity, Prediabetes
Recruiting
Neuromodulation for Metabolic Dysfunction
Spinal Cord Injuries (SCI), Prediabetes / Type 2 Diabetes
Not yet recruiting
Effects of Mango on Insulin Sensitivity in Prediabetes
Pre Diabetes
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rob Andrews, Prof principal investigator
University of Exeter
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Metformin Hydrochloride in people with Prediabetic State, run by University of Exeter at 5 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 16 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Between group difference in reduction of Homeostatic Model Assessment (HOMAR) of Insulin Resistance (IR, mass units). (time frame: 21 months (Stage1)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2018.