Sumatriptan (a drug used for the treatment of migraine) and blood sugar
| ISRCTN | ISRCTN13848689 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN13848689 |
| IRAS number | 277675 |
| Secondary identifying numbers | A095470, CPMS 47125, IRAS 277675 |
- Submission date
- 29/01/2021
- Registration date
- 01/02/2021
- Last edited
- 01/02/2021
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nutritional, Metabolic, Endocrine
Plain English summary of protocol
Background and study aims
Sumatriptan is a drug widely used for migraine treatment and data from mouse models show that it decreases appetite and lowers glucose. This glucose lowering effect of sumatriptan has not been studied in humans yet. In this study, we aim to establish in healthy overweight adults whether a single tablet of sumatriptan can improve:
1. sensitivity of the body to insulin (a hormone which regulates your blood glucose level), and/or
2. release of insulin from the pancreas
The results of this study might help design more targeted studies in people with diabetes. If ultimately proven effective, sumatriptan or similar treatments could be used in diabetes (including those treated with insulin as an “add-on” treatment) to improve glucose levels and reduce the risk of complications and substantial healthcare costs associated with this.
Who can participate?
Adults aged 18 – 65 years, who are overweight but otherwise healthy.
What does the study involve?
Participation will involve a screening visit (to determine if you are eligible) and 2 visits at which you will have a single dose of either sumatriptan or placebo (tablet without active drug) and studies with glucose and insulin infusion will be performed together with blood tests as detailed below. Drugs will be given in a random order (first sumatriptan and then placebo or vice versa) one at visit 1 and one at visit 2. This study is blinded so neither you nor the study doctors and nurses will know which tablet you had at which visit. This will allow us to assess the effects of the drug using a rigorous scientific approach. During the study you will be looked after by healthcare professionals (doctors and research nurses) trained in clinical research and the methods described below.
We wish to examine how the body handles glucose and insulin in overweight healthy volunteers (aged 18-65 years) after taking a single dose of sumatriptan or placebo. There will be three visits:
1. Screening visit
We will assess if you are eligible to participate by asking questions about your medical history, and performing a clinical examination. Your height and weight will be measured and a sample of your blood and urine will be taken. The results will be reviewed, and you will be informed if you are eligible to attend the subsequent visits. The visit is expected to take around 1 hour.
2. Visit 1
Visits will take place in the morning and you will need to come fasted (nothing to eat or drink except water from approximately 22:00 h the night before the visit). At the visit you will be given the assigned medication (sumatriptan or placebo). One intravenous cannula will be placed in each arm. The whole study visit will be performed over approximately 3 hours. You will first receive an infusion of glucose and blood samples will be taken at pre-defined time points (from the cannula). After 1 hour you will receive an infusion of insulin and blood samples will be taken at pre-defined time points. You will simultaneously receive an infusion of glucose to keep your blood glucose stable until the end of the procedure for the next 2 hours.
3. Visit 2
This is the same as Visit 1, the only difference being that the assigned medication will be the opposite of what you had at Visit 1 (i.e. if you had sumatriptan you will receive placebo and vice versa). All the visit procedures will be repeated as described in Visit 1 above.
At all visits you will be looked after by healthcare professionals (doctor and research nurses) trained in clinical research and the method described above. This study plan has been reviewed by our diabetes Patient and Public Involvement group (GRACED- Group for Research and Clinical Experience in Diabetes)- an independently chaired and functioning group established from volunteers attending the Wolfson Diabetes Endocrine Clinic in Cambridge.
What are the possible benefits and risks of participating?
Benefits: This study will not benefit you directly . However, the results of this study and your experience will help us develop targeted studies in people with diabetes to further explore the impact of sumatriptan on glucose levels in diabetic populations and if shown to be effective sumatriptan has the potential to be used as one of the treatment options in diabetes.
Risks: The procedure risks include. not being able to insert an intravenous cannula on the first attempt, bruising, skin irritation and infection. Well trained staff, standardised protocols and aseptic technique are used to minimise these risks. Other risks include well established side effects of sumatriptan. Side-effects of sumatriptan occurring between 1/100 to 1/10 people include: dizziness, sensation disturbance, temporary increase in blood pressure, flushing, shortness of breath, nausea and vomiting. However, the likelihood of these side-effects is very small given that only one dose is taken in this study and if these do occur they are likely to last for a short period. Glucose infusion may cause nausea and if this happens the procedure will be stopped. Furthermore, we would like to advise you not to take a type of drug called selective serotonin reuptake inhibitor (SSRI; used for the treatment of depression) immediately after the procedure as there is an extremely small risk of developing serotonin syndrome (high blood pressure, fast heart rate, increased temperature, tremor, sweating, diarrhoea) if sumatriptan and SSRI are used together. We will review your medication at each visit to identify any potential risk and advise you accordingly.
Where is the study run from?
University of Cambridge Transnational Research Facility (UK)
When is the study starting and how long is it expected to run for?
December 2020 to July 2021
Who is funding the study?
Diabetes Research and Wellness Foundation (UK)
Who is the main contact?
Dr Rajna Golubic, rg380@medschl.cam.ac.uk
Contact information
Scientific
MRC Wellcome Institute of Metabolic Science
Addenbrooke's Hospital
Cambridge
CB2 0QQ
United Kingdom
 ORCID ID |
0000-0003-0419-9582 |
|---|---|
| Phone | +44 (0)1223 74847 |
| rg380@medschl.cam.ac.uk |
Study information
| Study design | Random order double blinded placebo-controlled cross-over design |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised cross over trial |
| Study setting(s) | Other |
| Study type | Other |
| Participant information sheet | ISRCTN13848689_PIS_V2_01Nov2020.pdf |
| Scientific title | Effects of serotonin receptor agonism on blood glucose lowering: Proof of concept in humans |
| Study objectives | A single dose of sumatriptan (100 mg) significantly increases insulin sensitivity and/or insulin secretion compared to placebo. |
| Ethics approval(s) | Approved 04/12/2020, Camden and King's Cross Research Ethics Committee (Health Research Authority, Skipton House, 80 London Road, London, SE1 6LH, UK; +44 (0)207 104 8277; CamdenandKingsCross.REC@hra.nhs.uk), ref: 20/LO/1122 |
| Health condition(s) or problem(s) studied | Overweight adults with no known co-morbidities |
| Intervention | All subjects will undergo a screening visit. This will include an assessment of inclusion/exclusion criteria, physical exam, alcohol and substance screening test, pregnancy test for women and routine blood tests (full blood count, urea and electrolytes, HbA1C, liver function tests, blood borne viruses). The assessment of insulin sensitivity and insulin secretion usually requires separate study days. In this study, we aim to combine these into a single 3 hour physiological study combination (FSivGTT followed by a hyperinsulinaemic euglycaemic clamp (HEC) sometimes termed a “Botnia clamp”). Participants will attend 2 visits receiving either sumatriptan (100 mg) or placebo in a random order by a coin toss. At each visit the participant will arrive fasted. After taking either sumatriptan (100 mg) or placebo one intravenous cannula will be placed in each arm. Participants will receive an infusion of glucose and blood samples will be taken at pre-defined time points (from the cannula). After 1 hour particpatns will receive an infusion of insulin and blood samples will be taken at pre-defined time points. Participants will simultaneously receive an infusion of glucose to keep your blood glucose stable until the end of the procedure for the next 2 hours. There will be up to 4 weeks between visit 1 and visit 2. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Sumatriptan |
| Primary outcome measure | 1. Insulin sensitivity - expressed as M-value calculated from the hyperinsulinaemic euglycaemic clamp component of the Botnia clamp at visit 1 and visit 2 2. Insulin secretion - calculated from the frequently sampled intravenous glucose tolerance test component of the Botnia clamp at visit 1 and visit 2 |
| Secondary outcome measures | There are no secondary outcome measures |
| Overall study start date | 04/12/2020 |
| Completion date | 31/07/2021 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 10 to 12 |
| Key inclusion criteria | 1. Being able to provide written informed consent 2. Age between 18 and 65 years 3. Body Mass Index (BMI) ≥25 kg/m² and <30 kg/m² for non-Asian individuals; BMI ≥23 kg/m² and <25 kg/m² for Asian individuals according to the BMI classification by the World Health Organization (WHO) 4. HbA1C <48 mmol/mol at screening 5. Subject must not use any regular prescribed medications (this excludes simple analgesia used as needed) 6. Subject must not use any over the counter supplements targeting metabolism 7. Subject must not have any acute or chronic disease which in the opinion of the investigator may affect the study outcome 8. Subject must not be a current smoker 9. No history of substance abuse or excess alcohol consumption (>14 units/week) 10. Women of childbearing age must have a negative pregnancy test at screening and must not be breastfeeding 11. Women of childbearing age who are sexually active with a male partner must use highly effective contraceptive methods |
| Key exclusion criteria | 1. Use of any regular medications 2. Use of illicit drugs 3. Use of any over the counter supplements affecting metabolism 4. Diagnosis of any acute/chronic disease 5. Current smoking or excess alcohol consumption (>14 units/week) 6. Current pregnancy or lactation 7. Abnormal findings on physical exam or routine blood tests at screening (full blood count, urea and electrolytes, HbA1C, liver function tests) 8. Concurrent participation in another trial with an investigational product 9. History of anaphylaxis |
| Date of first enrolment | 04/01/2021 |
| Date of final enrolment | 01/06/2021 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Cambridge Biomedical Campus
Cambridge
CB2 0QQ
United Kingdom
Sponsor information
Hospital/treatment centre
Hills Road
Cambridge
CB2 0QQ
England
United Kingdom
| Phone | +44 (0)1223 256 620 |
|---|---|
| jacob.wingfield@addenbrookes.nhs.uk | |
| Website | http://www.cuh.org.uk/ |
"ROR" |
https://ror.org/04v54gj93 |
University/education
Insurance Section, Finance Division
University of Cambridge
Greenwich House
Madingley Rise
Madingley Road
Cambridge
CB3 0TX
England
United Kingdom
| Phone | +44 (0)1223 332 216 |
|---|---|
| insurance@admin.cam.ac.uk | |
| Website | http://www.cam.ac.uk/ |
|
"ROR" |
https://ror.org/013meh722 |
Funders
Funder type
Charity
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- Diabetes Research & Wellness Foundation, Diabetes Research and Wellness Foundation UK, DRWF
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/12/2021 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | The study protocol and the patient information sheet are made available via this website. Results will be published in peer-reviewed medical journals. Results in plain English will be published here. |
| IPD sharing plan | The current data sharing plans for this study are unknown and will be available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | version V2 | 01/11/2020 | 01/02/2021 | No | Yes |
| Protocol file | version V2 | 01/11/2020 | 01/02/2021 | No | No |
| HRA research summary | 28/06/2023 | No | No |
Additional files
- ISRCTN13848689_PIS_V2_01Nov2020.pdf
- uploaded 01/02/2021
- ISRCTN13848689_PROTOCOL_V2_01Nov2020.pdf
- uploaded 01/02/2021
Editorial Notes
01/02/2021: The participant information sheet was uploaded as an additional file. Uploaded protocol (not peer reviewed) Version 2, 01 November 2020.
29/01/2021: Trial’s existence confirmed by National Institute for Health Research (NIHR)
