Does the Hematopoietic Stem Cell Govern Residual Inflammatory Cardiovascular Risk in Type 2 Diabetes (DOTAFLAME)
Primary Purpose
Type 2 Diabetes
Status
Recruiting
Phase
Phase 4
Locations
Netherlands
Study Type
Interventional
Intervention
Semaglutide, 2.0 mg/mL
Sponsored by
About this trial
This is an interventional treatment trial for Type 2 Diabetes focused on measuring diabetes mellitus, dotatate, bone marrow, semaglutide, vascular inflammation, glp1
Eligibility Criteria
Inclusion Criteria:
- Age >50 years old
- Diagnosed with type 2 diabetes
- HbA1c >64mmol/mol
Exclusion Criteria:
- (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.
- Chronic or recent infections and/or clinical signs of infection and/or a plasma C-reactive protein above 10ng/ml
- Auto-immune diseases (including type 1 diabetes)
- Recent or chronic immunosuppressant or antibiotic usage
- Use of any GLP1R-agonist at baseline or prior intolerance to use of GLP1R-agonists.
- Inability or unwillingness to comply with the protocol requirements, or deemed by investigator to be unfit for the study.
- Uncontrolled hypertension (systolic blood pressure > 180mmHg, diastolic blood pressure > 100mmHg)
- Uncontrolled chronic inflammatory conditions, including gout.
- Women of childbearing age who are not using effective contraceptives.
- Heart failure New York Heart Association (NYHA) class IV at screening visit.
- 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.
- Pancreatitis in medical history.
Sites / Locations
- AMCRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment arm
Arm Description
Will receive semaglutide treatment for 6 months, at the highest tolerable dose, up to a maximum of 2.0mg weekly.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Full Information
NCT ID
NCT05597202
First Posted
October 14, 2022
Last Updated
May 8, 2023
Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Collaborators
Dutch Heart Foundation
1. Study Identification
Unique Protocol Identification Number
NCT05597202
Brief Title
Does the Hematopoietic Stem Cell Govern Residual Inflammatory Cardiovascular Risk in Type 2 Diabetes
Acronym
DOTAFLAME
Official Title
Does the Hematopoietic Stem Cell Govern Residual Inflammatory Cardiovascular Risk in Type 2 Diabetes
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 1, 2023 (Actual)
Primary Completion Date
March 2024 (Anticipated)
Study Completion Date
April 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Collaborators
Dutch Heart Foundation
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
Brief 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes
Keywords
diabetes mellitus, dotatate, bone marrow, semaglutide, vascular inflammation, glp1
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
22 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment arm
Arm Type
Experimental
Arm Description
Will receive semaglutide treatment for 6 months, at the highest tolerable dose, up to a maximum of 2.0mg weekly.
Intervention Type
Drug
Intervention Name(s)
Semaglutide, 2.0 mg/mL
Intervention Description
Semaglutide 2.0 mg/mL, administered subcutaneously once per week for a period of 6 months.
Primary Outcome Measure Information:
Title
Difference in coronary 68Ga-Dotatate uptake after treatment.
Description
The within subject comparison of 68Ga-Dotatate uptake in the coronary arteries before and after semaglutide treatment, expressed as a difference in TBRmax.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Difference in bone marrow aspirates after treatment.
Description
The within subject comparison of bone marrow aspirates before and after semaglutide treatment, expressed as a difference in stem cell count.
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age >50 years old
Diagnosed with type 2 diabetes
HbA1c >64mmol/mol
Exclusion Criteria:
(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.
Chronic or recent infections and/or clinical signs of infection and/or a plasma C-reactive protein above 10ng/ml
Auto-immune diseases (including type 1 diabetes)
Recent or chronic immunosuppressant or antibiotic usage
Use of any GLP1R-agonist at baseline or prior intolerance to use of GLP1R-agonists.
Inability or unwillingness to comply with the protocol requirements, or deemed by investigator to be unfit for the study.
Uncontrolled hypertension (systolic blood pressure > 180mmHg, diastolic blood pressure > 100mmHg)
Uncontrolled chronic inflammatory conditions, including gout.
Women of childbearing age who are not using effective contraceptives.
Heart failure New York Heart Association (NYHA) class IV at screening visit.
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.
Pancreatitis in medical history.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
R.F. Oostveen, MD
Phone
020 5667050
Email
r.oostveen@amsterdamumc.nl
Facility Information:
Facility Name
AMC
City
Amsterdam
State/Province
Noord-Holland
ZIP/Postal Code
1105AZ
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
R.F. Oostveen, MD
Phone
020 566 7050
Email
r.oostveen@amsterdamumc.nl
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Does the Hematopoietic Stem Cell Govern Residual Inflammatory Cardiovascular Risk in Type 2 Diabetes
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