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

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.

Study Overview

• Status: Recruiting
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Semaglutide, 2.0 mg/mL

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 22
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: R.F. Oostveen, MD; Phone Number: 020 5667050; Email: r.oostveen@amsterdamumc.nl

Study Locations

• Netherlands
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1105AZ
      • Recruiting
      • AMC
      • Contact: R.F. Oostveen, MD; Phone Number: 020 566 7050; Email: r.oostveen@amsterdamumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment arm; Will receive semaglutide treatment for 6 months, at the highest tolerable dose, up to a maximum of 2.0mg weekly.	Drug: Semaglutide, 2.0 mg/mL; Semaglutide 2.0 mg/mL, administered subcutaneously once per week for a period of 6 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Collaborators: Dutch Heart Foundation

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2023
• Primary Completion (Anticipated): March 1, 2024
• Study Completion (Anticipated): April 1, 2024

Study Registration Dates

• First Submitted: October 14, 2022
• First Submitted That Met QC Criteria: October 26, 2022
• First Posted (Actual): October 27, 2022

Study Record Updates

• Last Update Posted (Actual): May 9, 2023
• Last Update Submitted That Met QC Criteria: May 8, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: semaglutide; bone marrow; vascular inflammation; diabetes mellitus; dotatate; glp1
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: NL80519.018.22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No