Clinical trial NCT06976658: Glucokinase Activator in Monogenic Diabetes
Official title: Evaluating a Novel, Allosteric Glucokinase Activator in Monogenic Diabetes Secondary to Inactivating Glucokinase Mutations: a Randomised, Cross-over Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Diabetes Mellitus
Monogenic Diabetes
Keywords: GCK-MODY
glucokinase activator
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2025-05-16
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Evaluating a novel, allosteric glucokinase activator in monogenic diabetes secondary to inactivating glucokinase mutations: a randomised, cross-over trial

Detailed description: Evaluating a novel, allosteric glucokinase activator in monogenic diabetes secondary to inactivating glucokinase mutations: a randomised, cross-over trial

Eligibility criteria: Inclusion Criteria:

1. Age ≥18 and \<75 years
2. body mass index (BMI) \>18 and \<30 kg/m2
3. fasting plasma glucose \>5.6 mmol/L at screening
4. Participants with GCK-MODY had and are heterozygous carriers of a pathogenic or likely pathogenic GCK mutation at screening based on guidelines published by the American College of Medical Genetics and Genomics (ACMG), Association for Clinical Genomic Science (ACGS) and the ClinGen Monogenic Diabetes Expert Panel (MDEP) .

Exclusion Criteria:

1. Body weight \<45kg at screening
2. Current or planning pregnancy or lactating
3. troke or cardiovascular disease within 6 months of recruitment
4. severe renal dysfunction (estimated glomerular filtration rate \<30mL/min/1.73m2 or renal replacement therapy)
5. severe hepatic dysfunction (aspartate transaminase and/or alanine transaminase \> 3 times upper limit of normal)
6. history of drug abuse or excessive alcohol intake
7. severe hypoglycemia within 6 months prior to screening
8. anaemia with Hb \<10 g/dL at screening
9. excessive blood loss \>300mL within 1 month of screening
10. use of strong or moderate CYP3A4 inhibitors or inducers
11. use of sulfonylureas, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 agonists, sodium glucose transporter 2 inhibitors, insulin, thiazolidinediones, acarbose in the 6 weeks prior to randomisation
12. use of long-term high-dose corticosteroids at randomisation
13. serious concurrent infections at time of screening

Primary outcomes:
measure: Fasting plasma glucose
timeFrame: 8 weeks
Secondary outcomes:
measure: • HbA1c
timeFrame: 8 weeks
measure: CGM metrics time in range
timeFrame: 8 weeks
measure: CGM metric coefficient of variation
timeFrame: 8 weeks
measure: Glucose area under the curve during OGTT
timeFrame: 8 weeks
measure: Insulin area under the curve during OGTT
timeFrame: 8 weeks
measure: GLP1 area under the curve during OGTT
timeFrame: 8 weeks
Other outcomes:
measure: Treatment-emergent adverse events
timeFrame: 8 weeks
measure: Hypoglycemia
timeFrame: 8 weeks
measure: Blood pressure
timeFrame: 8 weeks
measure: Body weight
timeFrame: 8 weeks
measure: Renal and liver function tests
timeFrame: 8 weeks
measure: Lipid profile
timeFrame: 8 weeks
Locations:
city: Hong Kong
country: Hong Kong
facility: 3M, Diabetes and Endocrine Research Center
Study officials:
References: