Sumatriptan and Glucose

Sponsor

Cambridge University Hospitals NHS Foundation Trust (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04690270

Collaborator

(none)

Enrollment

Location

Arms

5.7

Anticipated Duration (Months)

2.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Overweight	Drug: Sumatriptan 100 mg	Early Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

12 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jan 4, 2021

Anticipated Primary Completion Date :

Jun 25, 2021

Anticipated Study Completion Date :

Jun 25, 2021

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Being able to provide a written informed consent
Age between 18 and 65 years
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)
HbA1C<48 mmol/mol at screening
Subject must not use any regular prescribed medications (this excludes simple analgesia used as needed)
Subject must not use any over the counter supplements targeting metabolism
Subject must not have any acute or chronic disease which in the opinion of the investigator may affect the study outcome
Subject must not be a current smoker
No history of substance abuse or excess alcohol consumption (>14 units/week)
Women of childbearing age must have a negative pregnancy test at screening and must not be breastfeeding
Women of childbearing age who are sexually active with a male partner must use highly effective contraceptive methods

Exclusion Criteria:

Use of any regular medications
Use of illicit drugs
Use of any over the counter supplements affecting metabolism
Diagnosis of any acute / chronic disease
Current smoking or excess alcohol consumption (>14 units/week)
Current pregnancy or lactation
Abnormal findings on physical exam or routine blood tests at screening (full blood count, urea and electrolytes, HbA1C, liver function tests)
Concurrent participation in another trial with an investigational product
History of anaphylaxis