Aniracetam for prevention of hypoglycemia in type 1 diabetes
| ISRCTN | ISRCTN95901685 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN95901685 |
| IRAS number | 349276 |
- Submission date
- 07/02/2025
- Registration date
- 22/04/2025
- Last edited
- 22/04/2025
- Recruitment status
- Not yet recruiting
- Overall study status
- Ongoing
- Condition category
- Nutritional, Metabolic, Endocrine
Plain English Summary
Background and study aims
Type 1 diabetes (T1D) requires lifelong insulin therapy. Hypoglycaemia (low blood sugar) is a common and potentially life-threatening complication of insulin treatment. Despite advances in insulin types and delivery methods, hypoglycaemia remains a significant side effect, contributing to impaired quality of life for patients and their loved ones, and increased healthcare costs.
Hypoglycaemia poses significant risks including confusion, seizures, and coma. Recurrent hypoglycaemia can lead to hypoglycaemia unawareness; usually people who are treated with insulin are aware that their blood sugar is low and can take action to treat this (by consuming fast acting sugar). People who have hypoglycaemia unawareness do not have symptoms or signs, therefore their diabetes management is more complicated and they are at a much higher risk of severe hypoglycaemic events, including seizures and coma.
By investigating a supplement that counteracts the underlying mechanisms of hypoglycaemia, we have the potential to improve hypoglycaemia management and the quality of life for individuals with type 1 diabetes. There is no current preventative treatment for insulin induced hypoglycaemia. Current treatment strategies for hypoglycemia in type 1 diabetes primarily involve glucose monitoring and administration of glucose or glucagon. However, these approaches may not always be effective in preventing or resolving hypoglycemic episodes, especially if there is hypoglycaemia unawareness.
There is a need for treatments that can complement existing treatments to provide more targeted management of hypoglycemia in individuals with type 1 diabetes, and a need for treatments that can prevent the disabling and dangerous side effect of hypoglycaemia.
This study is investigating the effects of the supplement aniracetam during hypoglycaemia in individuals with T1D. Scientific studies so far lead us to think that supplementation with aniracetam will lead to improved control, a reduction in hypoglycaemic episodes, and, in the future, enhanced overall well-being in participants with type 1 diabetes.
Who can participate?
People aged 21-70 who have had Type 1 diabetes for 5 years or more.
What does the study involve?
This study involves three visits to Edinburgh Royal clinical research facility for one screening visit, including blood tests, then two hypoglycaemic clamp studies, separated over one to two months. This clamp study is safe and well recognised in the field of diabetes research. It involves a 6 hour visit where blood glucose is carefully and slowly lowered into low blood glucose levels (hypo) to measure, using blood tests, the body's response to this. One clamp will test the body's response alone and one will test the body's response using aniracetam.
What are the possible benefits and risks of participating?
Benefits. If the results are positive this will change diabetes management. This has the potential to reduce the disabling and dangerous side effect of insulin therapy: Hypoglycaemia.
Risks. There are no risks. The clamp study is considered safe and is the gold standard procedure used in research.
Where is the study run from?
The Edinburgh Clinical Research Facility, Scotland (UK)
When is the study starting and how long is it expected to run for?
October 2024 to December 2027
Who is funding the study?
The Helmsley Charitable Trust (USA)
Who is the main contact?
Professor Shareen Forbes, Shareen.Forbes@ed.ac.uk
Contact information
Public, Scientific, Principal Investigator
University of Edinburgh, BHF Centre for Research Excellence, Queen's Medical Research Institute, 47 Little France Crescent
Edinburgh
EH16 4TJ
United Kingdom
 ORCID ID |
0000-0002-9127-0641 |
|---|---|
| Phone | +44 1312426736 |
| Shareen.Forbes@ed.ac.uk |
Scientific
University of Edinburgh, BHF Centre for Research Excellence, Queens Medical Research Institute, 47 Little France Crescent
Edinburgh
EH16 4TJ
United Kingdom
| Phone | +44 1312426736 |
|---|---|
| Nicola.Baillie@ed.ac.uk |
Study information
| Study design | Randomised controlled exploratory physiological clinical trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Other |
| Participant information sheet | Not available in web format. Please use contact details to request a participant information sheet. |
| Scientific title | Repurposing positive allosteric modulators of glutamate receptors to prevent hypoglycemia in type 1 diabetes: a pilot clinical study |
| Study acronym | APHiD |
| Study hypothesis | We hypothesise that aniracetam, a positive allosteric modulator of the α-cell AMPA/kainate receptors, can increase the counterregulatory response of glucagon in response to hypoglycaemia in people with T1D. |
| Ethics approval(s) |
Not yet submitted 20/02/2025, South East Scotland Research Ethics Committee 1 (NHS Lothian, Waverley Gate, 2 - 4 Waterloo Place, Edinburgh, EH1 3EG, United Kingdom; +44 131465 5473; Sandra.Wyllie@nhslothian.scot.nhs.uk) |
| Condition | Type 1 Diabetes |
| Intervention | This is a double blind, crossover, placebo controlled, exploratory physiological study. It is a single site study on 18 participants with T1D, who will be recruited over a 12 month period. The aim is to recruit 9 male and 9 female participants. Each participant will undergo two hypoglycaemic clamp studies, one study will analyse the body's response to Aniracetam 1500mg, the standard dose used in Europe, given during the clamp. The second study, 4-6 weeks later, will analyse the same parameters using the identical placebo. An NHS clinical trials pharmacist will be unblinded and therefore keep a record of which intervention each participant has had. |
| Intervention type | Other |
| Primary outcome measure | Glucagon, measured during insulin clamp procedures |
| Secondary outcome measures | Cortisol, Adrenaline, Noradrenaline, Insulin and Glucose concentrations, measured during insulin clamp procedures |
| Overall study start date | 01/10/2024 |
| Overall study end date | 01/12/2027 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 21 Years |
| Upper age limit | 65 Years |
| Sex | Both |
| Target number of participants | 18 |
| Participant inclusion criteria | 1. Participants with T1D with C-peptide levels less than 100pmol/L 2. Age 21-65 years 3. T1D for 5 years or more |
| Participant exclusion criteria | 1. Proliferative retinopathy 2. History of Diabetic ketoacidosis in the preceding 6 months 3. Severe hypoglycaemic episode requiring external assistance in the preceding 6 months 4. History of Haemophilia, Cystic Fibrosis, pancreatic disease or complete pancreatectomy, ischaemic heart disease, cardiac arrhythmia, epilepsy or hypoglycaemia induced seizure 5. History of severe reaction or allergy to adhesive necessary to this study 6. Unable to adhere to study timetable 7. Unable to give informed consent 8. Pregnancy or planning pregnancy. We will perform a pregnancy test on all eligible participants at baseline 9. Concurrent use of any non-insulin glucose-lowering agent (including GLP-1 agonists, Symlin, DPP-4 inhibitors, SGLT-2 inhibitors, sulfonylureas). These may lower insulin requirements and predispose to diabetic ketoacidosis 10. Hypothyroidism 11. Concurrent use of medication that may affect blood glucose such as SSRIs 12. Inability to understand or speak English. Time is of the essence during the clamp procedure, there is no time for translation 13. A condition, which in the opinion of the investigator, would put the patient or study at risk |
| Recruitment start date | 01/07/2025 |
| Recruitment end date | 01/07/2027 |
Locations
Countries of recruitment
- Scotland
- United Kingdom
Study participating centre
Edinburgh
EH16 4SA
United Kingdom
Sponsor information
Charity
230 Park Avenue
New York
NY 1016
United States of America
| Phone | +1(212) 679-3600 |
|---|---|
| grants@helmsleytrust.org | |
| Website | http://helmsleytrust.org/ |
"ROR" |
https://ror.org/011x6n313 |
Funders
Funder type
Charity
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- Helmsley Charitable Trust, The Leona M. and Harry B. Helmsley Charitable Trust, Leona M. & Harry B. Helmsley Charitable Trust, The Helmsley Charitable Trust
- Location
- United States of America
Results and Publications
| Intention to publish date | 01/06/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Stored in non-publicly available repository |
| Publication and dissemination plan | Results will be published in a peer reviewed journals. Results will be disseminated at external and internal conferences and meetings. |
| IPD sharing plan | The data sharing plans for the current study are unknown and will be made available at a later date |
Editorial Notes
07/02/2025: Trial's existence confirmed by Leona M. and Harry B. Helmsley Charitable Trust.
