The GAPSID Study - How GLP-1 Analogues Prevent Steroid-Induced Diabetes

NCT ID: NCT06318442

Last Updated: 2024-10-02

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-05-15
• Study Completion Date: 2027-06-01

Brief Summary

TITLE: How GLP-1 Analogues prevent steroid-induced diabetes (The GAPSID Study)

DESIGN: A double-blind study evaluating how GLP-1 analogues, compared with metformin, prevent hyperglycaemia in response to a 7-day course of dexamethasone (DEX) 6 mg once daily. This is a mechanistic experimental medicine study.

AIMS: To evaluate the mechanisms by which GLP-1 analogues reduce steroid-induced hyperglycaemia compared to metformin.

OUTCOME MEASURES:

• Primary: Glucose tolerance in response to standardised mixed meal test (MMT) lasting for 240 minutes, measured in all participants at baseline and on day 7 DEX.
• Secondary: Indices of insulin resistance (M-value), beta-cell function (acute insulin response to glucose) and disposition, as measured by a combined IV glucose tolerance test and hyperinsulinaemic-euglycaemic clamp, performed at baseline and on day 7 DEX.
• Exploratory: Tissue specific changes in adipose AMPK determined from adipose and muscle biopsies, taken from a subset of approximately 8 individuals in each group.

ELIGIBILITY: People living with pre-diabetes or lifestyle controlled diabetes

STUDY DURATION: This study will take place over 3 weeks for each partcipant. Study procedures include 10 days of baseline continuous glucose monitoring (CGM) followed by 7 days of dexamethasone with GLP-1, metformin or placebo. Participants will attend a follow-up visit 3-5 days after completing the 7-day course of study drug. The study will run over a period of 3 years.

ANTICIPATED IMPACT: Mechanistic evidence for the use of GLP-1 analogues, compared with metformin, in the treatment of steroid-induced diabetes.

Conditions

Steroid-Induced Diabetes; Steroid Induced Hyperglycemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Once daily semaglutide

Once daily semaglutide 3 mg (uptitrated to 3 mg twice daily after two days).

Group Type: EXPERIMENTAL

Semaglutide Oral Product

Intervention Type: DRUG

Oral semaglutide 3mg once uptitrated to twice daily

- Metformin

Metformin modified release tablets (500mg once daily for the first two days, then 500 mg twice daily).

Group Type: ACTIVE_COMPARATOR

Metformin Oral Tablet

Intervention Type: DRUG

Metformin modified release tablets 500mg once daily uptitrated to twice daily).

Placebo

Placebo tablets

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo tablets

Interventions

Semaglutide Oral Product

Oral semaglutide 3mg once uptitrated to twice daily

Intervention Type: DRUG

Metformin Oral Tablet

Metformin modified release tablets 500mg once daily uptitrated to twice daily).

Intervention Type: DRUG

Placebo

Placebo tablets

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Adults ≥ 18 years;
• Male or female;
• Pre-diabetes (HbA1c ≥42 and <47 mmol/mol, or lifestyle-controlled diabetes (HbA1c ≥48 and ≤52 mmol/mol); measurements within range on two separate occasions ≥90 days apart)
• Body mass index ≥22.5 kg/m2

Exclusion Criteria

• Prior treatment with any diabetes medication within 90 days;
• Current or planned pregnancy, or current breastfeeding;
• Previous treatment with GC (topical, oral, injected) within 30 days or 90 days for extended-release injected GCs (e.g. Depo-Medrone);
• Continuing requirement for GC treatment (e.g. for steroid replacement, chronic inflammatory or immunological condition);
• Treatment with medications altering DEX pharmacokinetics (e.g. phenytoin, carbamazepine, ritonavir).
• History of pancreatitis, renal disease (eGFR <30), severe hepatic impairment, gallbladder disorders, or GI disease (e.g. IBD), heart failure, history of medullary thyroid cancer (MTC), or previous skin reactions.
• History of bleeding disorders of anticoagulant therapies (exclusion from the biopsy substudy only)
• History of giving blood or having taken part in another non-related study in the last three months
• History of any other medical, psychological condition, or use of any medications, which, in the opinion of the investigators, would either interfere with the study or compromise the safety of the participant.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Imperial College London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Karim Meeran

Role: PRINCIPAL_INVESTIGATOR

Imperial College London

Locations

Imperial College Healthcare NHS Trust

London, , United Kingdom

Site Status: RECRUITING

Countries

United Kingdom

Central Contacts

Katharine Lazarus, MBChB, BSc

Role: CONTACT

k.lazarus@imperial.ac.uk

07555717544

Other Identifiers

22HH8018

Identifier Type: -

Identifier Source: org_study_id