Clinical trial NCT06318442: The GAPSID Study - How GLP-1 Analogues Prevent Steroid-Induced Diabetes
Official title: How GLP-1 Analogues Prevent Steroid-Induced Diabetes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Steroid-Induced Diabetes
Steroid Induced Hyperglycemia
Lead sponsor: Imperial College London
Sponsor class: OTHER
First posted: 2024-03-19
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


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.

Primary outcomes:
measure: Difference in Glucose tolerance
timeFrame: Through study completion, on day 7 dexamethasone and study medication
Secondary outcomes:
measure: Difference in insulin secretion
timeFrame: Day 6 of dexamethasone and study medication
measure: Difference in insulin sensitivity
timeFrame: Day 6
measure: Difference in insulin sensitivity
timeFrame: Day 6
measure: Difference in insulin sensitivity
timeFrame: Day 6
Other outcomes:
measure: Mean glucose and glycaemic variation by continuous glucose monitoring (CGM), using a validated blinded system (Dexcom G7).
timeFrame: Through study completion
measure: Changes in fasting gut hormones
timeFrame: Through study completion, on day 7 dexamethasone and study medication
measure: Changes in fasting gut hormones
timeFrame: Through study completion, on day 7 dexamethasone and study medication
measure: Changes in fasting gut hormones
timeFrame: Through study completion, on day 7 dexamethasone and study medication
measure: Changes in fasting lipid profile
timeFrame: Through study completion, on day 7 dexamethasone and study medication
measure: Changes in post prandial gut hormones
timeFrame: Through study completion, on day 7 dexamethasone and study medication
measure: Changes in post prandial gut hormones
timeFrame: Through study completion, on day 7 dexamethasone and study medication
measure: Changes in anthropometrics
timeFrame: Through study completion, on day 7 dexamethasone and study medication
measure: Changes in anthropometrics
timeFrame: Through study completion, on day 7 dexamethasone and study medication
measure: Tissue specific changes in AMPK determined from adipose and muscle biopsies
timeFrame: Through study completion, on day 7 dexamethasone and study medication
Locations:
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
Study officials:
affiliation: Imperial College London
name: Karim Meeran
role: PRINCIPAL_INVESTIGATOR
References: