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

Type 2 Diabetes Clinical Trial

— DOTAFLAME  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05597202
• Other study ID #: NL80519.018.22
• Status: Recruiting
• Phase: Phase 4
• Start date: January 1, 2023
• Est. completion date: April 2024

Study information

• Verified date: May 2023
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: R.F. Oostveen, MD
• Phone: 020 5667050
• Email: r.oostveen[@]amsterdamumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 22
• Est. completion date: April 2024
• Est. primary completion date: March 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• Semaglutide, 2.0 mg/mL
Semaglutide 2.0 mg/mL, administered subcutaneously once per week for a period of 6 months.

Locations

Country	Name	City	State
Netherlands	AMC	Amsterdam	Noord-Holland

Sponsors (2)

Lead Sponsor	Collaborator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)	Dutch Heart Foundation

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference in coronary 68Ga-Dotatate uptake after treatment.	The within subject comparison of 68Ga-Dotatate uptake in the coronary arteries before and after semaglutide treatment, expressed as a difference in TBRmax.	6 months
Secondary	Difference in bone marrow aspirates after treatment.	The within subject comparison of bone marrow aspirates before and after semaglutide treatment, expressed as a difference in stem cell count.	6 months