Does the Hematopoietic Stem Cell Govern Residual Inflammatory Cardiovascular Risk in Type 2 Diabetes (DOTAFLAME)

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Status and phase: Enrolling; Phase 4

Conditions: Type 2 Diabetes

Treatments: Drug: Semaglutide, 2.0 mg/mL

Study type: Interventional

Funder types: Other

Identifiers

NCT05597202

NL80519.018.22

Details and patient eligibility

About

To study the effect of type 2 diabetes (T2D) on vascular wall inflammation and hematopoietic stem cell composition in vivo, and whether these changes can be reversed with glucagon like peptide 1 receptor (GLP1R)-agonism.

Full description

We will use 68Ga-Dotatate PET/CT scans, bone marrow aspirations and peripheral blood analyses to determine the effect of type 2 diabetes on vascular wall inflammation, and hematopoietic stem cell composition, and whether these changes can be reversed using high dose semaglutide treatment, up to 2.0mg subcutaneously per week, for a period of six months.

Enrollment: 22 estimated patients

Sex: All

Ages: 50+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age >50 years old
• Diagnosed with type 2 diabetes
• HbA1c >64mmol/mol

Exclusion criteria

1. (History of) malignant diseases or any clinically significant medical condition that could interfere with the conduct of the study in the opinion of the investigator.
2. Chronic or recent infections and/or clinical signs of infection and/or a plasma C-reactive protein above 10ng/ml
3. Auto-immune diseases (including type 1 diabetes)
4. Recent or chronic immunosuppressant or antibiotic usage
5. Use of any GLP1R-agonist at baseline or prior intolerance to use of GLP1R-agonists.
6. Inability or unwillingness to comply with the protocol requirements, or deemed by investigator to be unfit for the study.
7. Uncontrolled hypertension (systolic blood pressure > 180mmHg, diastolic blood pressure > 100mmHg)
8. Uncontrolled chronic inflammatory conditions, including gout.
9. Women of childbearing age who are not using effective contraceptives.
10. Heart failure New York Heart Association (NYHA) class IV at screening visit.
11. Active liver disease or hepatic dysfunction, defined as aspartate aminotransferase (ASAT) or alanine aminotransferase (ALAT) ≥ 2 times the upper limit of normal (ULN) at screening visit.
12. Pancreatitis in medical history.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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22 participants in 1 patient group

Treatment arm

Experimental group

Description:

Will receive semaglutide treatment for 6 months, at the highest tolerable dose, up to a maximum of 2.0mg weekly.

Treatment:

Drug: Semaglutide, 2.0 mg/mL