Sumatriptan and Glucose

Effects of Serotonin Receptor Agonism on Blood Glucose Lowering: Proof of Concept in Humans

The purpose of this study is to establish the proof of concept for a brain serotonin pathway controlling blood glucose control in humans. We will examine whether activation of serotonin receptors by a single dose of sumatriptan (a drug used for the treatment of migraine) can lead to short term changes in blood glucose homeostasis. Thus far, this has been shown only in animal models but no study in humans has directly investigated this research question.

Briefly, in this study we will give a single dose of sumatriptan (100 mg) to each participant in a small sample (10 to 12) of overweight or obese, otherwise healthy humans. It will take place in the Translational Research Facility which is embedded in the Cambridge University Hospitals NHS Foundation Trust. The research staff have extensive experience and expertise in the procedures which will be used. The study will involve a screening visit and 2 subsequent visits at which sumatriptan/placebo will be taken and the glucose metabolism will be assessed using a Botnia clamp (3h procedure involving insulin and glucose infusions given intravenously with frequent blood sampling to assess insulin secretion and sensitivity). There will be about 60 days between screening visit and the last visit. The entire study (including the recruitment and data analysis) is expected to complete in about 12 months.

If sumatriptan alters glucose control, this might support future testing in disease models i.e. people with type 1 diabetes (T1D) and/or type 2 diabetes (T2D). Ultimately, if successful, either sumatriptan could be repurposed and/or other drugs from this group (triptans) could be developed for diabetes.

Study Overview

• Status: Unknown
• Conditions: Overweight
• Intervention / Treatment: Drug: Sumatriptan 100 mg

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Rajna Golubic, MD, PhD; Phone Number: 01223748471; Email: rg380@medschl.cam.ac.uk
• Study Contact Backup: Name: Jane Kennet, MD, FRCP; Phone Number: 01223748471; Email: jk605@cam.ac.uk

Study Locations

• United Kingdom
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
      • Rajna Golubic
      • Contact: Rajna Golubic, MD, PhD; Phone Number: 01223748471; Email: rg380@medschl.cam.ac.uk
      • Contact: Jane Kennet; Phone Number: 01223748471; Email: jk605@cam.ac.uk
      • Principal Investigator: Mark Evans, MD, FRCP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Being able to provide a 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 and 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

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Sumatriptan 100 mg; Given the cross-over design all participants will receive both sumatriptan (100 mg, single dose) and placebo in a random order.	Drug: Sumatriptan 100 mg; Single dose Sumatriptan 100 mg; Other Names: Example of a brand name for sumatriptan: Migratan
PLACEBO_COMPARATOR: Placebo; Given the cross-over design all participants will receive both sumatriptan (100 mg, single dose) and placebo in a random order.	Drug: Sumatriptan 100 mg; Single dose Sumatriptan 100 mg; Other Names: Example of a brand name for sumatriptan: Migratan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin sensitivity	Change in M-value from the hyperinsulinaemic euglycaemic clamp from visit 2 to visit 3 between sumatriptan and placebo	1 to 4 weeks
Insulin secretion	Change in first phase insulin response from the intravenous glucose tolerance test from visit 2 to visit 3 between sumatriptan and placebo	1 to 4 weeks

Collaborators and Investigators

• Sponsor: Cambridge University Hospitals NHS Foundation Trust
• Investigators: Study Chair: Mark Evans, Institute of Metabolic Science, Hills Road, CB2 0QQ, Cambridge, UK

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): January 4, 2021
• Primary Completion (ANTICIPATED): June 25, 2021
• Study Completion (ANTICIPATED): June 25, 2021

Study Registration Dates

• First Submitted: December 27, 2020
• First Submitted That Met QC Criteria: December 27, 2020
• First Posted (ACTUAL): December 30, 2020

Study Record Updates

• Last Update Posted (ACTUAL): December 30, 2020
• Last Update Submitted That Met QC Criteria: December 27, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: insulin sensitivity; type 2 diabetes; type 1 diabetes; insulin secretion; glucose homeostasis; serotonin agonism
• Additional Relevant MeSH Terms: Body Weight; Overweight; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Serotonin Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Vasoconstrictor Agents; Sumatriptan
• Other Study ID Numbers: A095470; 277675 (OTHER: IRAS)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No