Maturity Onset Diabetes of the Young
Conditions
Brief summary
The reason for this research study is to better understand the use of liraglutide, a commonly prescribed Type 2 diabetes medication, in patients with a diagnosis of maturity-onset diabetes of the young (MODY). The investigators are interested in better understanding the way that this drug affects the metabolism and hormone levels of a person with MODY. Many people with MODY report having gastrointestinal (GI) issues such as an upset stomach. Investigators also are interested in finding out if this drug will help with GI issues. If liraglutide does help with this symptom of MODY, the investigators want to know why this happens. If this drug is effective for participants, the investigators will use participants cells to make human induced pluripotent stem cell (iPSC). This means that the investigators will use participant cells to create what are called stem cells, which are cells in the body that are able to be told what their job is. Investigators will use these cells to see what happens in gastrointestinal (GI) tract.
Detailed description
The objective of this study is to perform a comprehensive metabolic and hormonal evaluation of individuals with Maturity-onset diabetes of the young (MODY) at baseline and then assess response to initiation of liraglutide. Select individuals will be consented for human induced pluripotent stem cell (iPSC) generation to identify the cellular basis of enteroendocrine cell (EEC) dysfunction. The hypothesis is that heterozygous mutations in MODY-related genes contribute to a range of GI pathologies, including regional disruptions in epithelial identity and disturbances in the function of EECs. Thus, patients with MODY may experience improvement not only in HbA1c and BMI but also in GI symptoms with initiation of GLP-1 receptor agonists. Investigators plan to enroll approximately 50 patients with MODY and obtain baseline metabolic labs and imaging along with enteroendocrine labs before initiating liraglutide and assessing response with repeat labs and imaging. This project will provide further guidance for clinical care and treatment of patients with MODY.
Interventions
DRUGLiraglutide
Liraglutide will be prescribed following FDA approved packet insert for type 2 diabetes in our test population.
Sponsors
Mansa
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
10 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of MODY via genetic testing * HgbA1c \>6.5%
Exclusion criteria
* History of anaphylaxis to GLP-1 receptor agonists * Already taking GLP-1 receptor agonists * on medications within the stimulant class * have had bariatric surgery * personal or family history of cancer, especially medullary thyroid cancer * personal history of pancreatitis or pathogenic variants associated with increased risk of pancreatitis * known active kidney disease * severe hypoglycemia (glucose \< 50 mg/dL) within 3 months of study enrollment * HbA1c \> 10.0% * episode of diabetic ketoacidosis (DKA) in the past 3 months * are currently pregnant * BMI \< 18.5 kg/m2 and pediatric patients with BMI \< 5th percentile
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Blood sugar control - HbA1C | Baseline and 3 months after study treatment initiation | Hemoglobin A1c |
| BMI | baseline, 1 month, 2 months, and final study visit 3 months after study treatment initiation | Body mass index; weight and height will be combined to report BMI in kg/m\^2 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Enteroendocrine function - insulin | baseline and 3 months after study treatment initiation | Fasting and post meal blood serum insulin levels will be assessed |
| Enteroendocrine function - c-peptide | baseline and 3 months after study treatment initiation | Fasting and post meal blood serum c-peptide levels will be assessed |
| Metabolic - Blood Sugar | Baseline through three months of study treatment | Glycemic patterns observed utilizing a continuous glucose monitor |
| Liver steatosis | baseline and 3 months after treatment initiation | MRI to determine liver health |
| Body fat percentage | baseline, 1 month, 2 months, and final study visit 3 months after study treatment initiation | % body fat as identified by DXA |
| Enteroendocrine function - GI symptoms | baseline, 1 month, 2 months, and final study visit 3 months after study treatment initiation | ANMS Gastroparesis Cardinal Symptom Index Daily Diary (ANMS GCSI-DD) |
Countries
United States
Contacts
Primary ContactMansa Krishnamurthy, M.D.
Outcome results
None listed