Primary objectives: To assess the extent of vascular wall inflammation in DM type 2 patients and the residual risk after 3 months of high dosage statin therapy, as measured with 68Ga-Dotatate PET-CT. Secondary objectives: To assess the feasibility…
ID
Source
Brief title
Condition
- Diabetic complications
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameter will be difference in arterial wall inflammation,
expressed as target-to-background ratio (TBR) in the carotid, coronary arteries
and aorta, after three months of statin therapy.
Secondary outcome
We will assess any possible differences in systemic inflammatory state by
measuring 68Ga-Dotatate uptake in spleen and bone-marrow.
Background summary
Patients with diabetes mellitus (DM) have an over tenfold lifetime risk for
cardiovascular disease (CVD). In recent years we have acquired vast experience
with 18F-FDG PET-CT to visualize and quantify arterial wall inflammation.
However, 18F-FDG reflects glucose metabolism only and lacks the ability to
visualize specific cellular involvement. In addition in DM patients,
hyperglycaemia and hyperinsulinemia may hamper 18F-FDG image contrast thereby
reducing sensitivity of inflammation assessment. 68Ga-Dotatate is a PET tracer
with a high affinity for the somatostatin receptor subtype 2 (SSTR2) commonly
associated with neuroendocrine tumours but also expressed on activated
macrophages. 68Ga-Dotatate has recently been validated as a marker of
atherosclerotic inflammation in patients with established CVD. Whether
68Ga-Dotatate PET-CT may serve as a novel more specific imaging procedure for
the in vivo evaluation therapies targeting vascular wall inflammation is
unknown. It has been shown that statin therapy leads to a rapid and
dose-dependent reduction in 18F-FDG uptake. Therefore, it is highly interesting
to use statin therapy (as golden standard) to longitudinally validate
68Ga-Dotatate PET/CT scanning as an imaging procedure to evaluate the residual
risk as a basis for the in vivo evaluation of novel therapies targeting
vascular inflammation.
Study objective
Primary objectives: To assess the extent of vascular wall inflammation in DM
type 2 patients and the residual risk after 3 months of high dosage statin
therapy, as measured with 68Ga-Dotatate PET-CT. Secondary objectives: To assess
the feasibility to measure splenic and bone-marrow inflammatory activity with
68Ga-Dotatate PET-CT in DM patients.
Study design
This study is designed as a single-centre intervention study, which will
consist of a group of DM patients. After screening for eligibility, subjects
will undergo cardiovascular risk assessment, laboratory testing and
68Ga-Dotatate PET-CT. Thereafter, patients will be treated with atorvastatin
40mg once daily for three months after which 68Ga-Dotatate PET-CT and
laboratory testing will be repeated.
Study burden and risks
The results of this study will contribute to the development of a novel imaging
procedure which can be used as a specific modality for the assessment of
vascular plaque inflammation and its reversibility. Such imaging modalities can
be used in the future as a more specific surrogate endpoints for the assessment
of novel anti-atherosclerotic treatment in DM patients at risk of CVD.
Currently, novel drugs targeting the inflammatory component of atherosclerotic
vascular disease are being developed. Our study can help to lead to a clear
molecular insight in the mechanism of novel treatment as well as to ways to
differentiate between DM patients who will and who are unlikely to benefit from
such treatments.
Patients enrolling in this study do not have direct benefit by participating in
this study. The burden and risks of participating in this study are estimated
to be medium, it requires a maximum of three visits and a telephone
consultation. The imaging procedure will be conducted with an established
radiopharmaceutical (68Ga-Dotatate), validated for vascular imaging, which is
routinely used in the AMC for clinical purpose and does not have any
side-effects when used in the proposed dosage. Treatment of DM patients with
atorvastatin 40mg is first choice treatment and conform international
guidelines. However, extra attention will be paid to prevent any serious statin
related side-effects. 68Ga-Dotatate PET-CT related radiation exposure is
estimated to have a maximum of 7.6 mSv. This corresponds to a category IIb risk
according to the NCS *Radiation Dose and Risk Estimates* report (NCS report
2016, page 16). As this study is primarily intended for the development of a
novel imaging procedure with an established radiopharmaceutical, we believe
this radiation dosage is justified.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
Patients:
1. Aged 50 years and older
2. Diagnosed with diabetes mellitus type 2 and using oral glucose lowering
therapy, insulin or combined glucose lowering therapy.
3. Not on statin therapy or willing to stop with current statin therapy for 6
weeks prior to visit 2.
4. HbA1c values below 65 mmol/L.
5. Patients with *stable* diabetes mellitus, i.e. no changes in type of glucose
lowering therapy and / or dosage of oral glucose lowering therapy in the past
three months. No more than 20% change in dosage of insulin therapy (short and
long acting) in the last three months.
Exclusion criteria
- History of cardiovascular disease (previous CV-event (MI / stroke) or known
coronary artery disease (including acute coronary syndrome).
- History of chronic kidney disease stage 3b - 5, defined as a CKD-EPI value of
< 45 ml/min/1,73m2.
- 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 (< 1 month) infections and/or clinical signs of acute
infection and/or CRP > 10 mg/L.
- History of auto-immune diseases.
- Standard contra-indications to 68Ga-Dotatate PET, and CT based on physicians
experience and current practices.
- Inability or unwillingness to comply with the protocol requirements, or
deemed by investigator to be unfit for the study.
- Planned radiation exposure in the next year due to participation in a
research project with radiation exposure or for clinical reasons.
- Elevated liver enzymes (> 2 ULN of liver transaminases), acute liver
failure or known liver disease.
- Prior medium to severe statin-related side effects or statin related
hypersensitivity, i.e. (severe) muscle pains with and/or without myopathy .
- The concomitant use of statin contra-indicated drugs, including the use of
CYP3A4 inhibitors (i.e. erytromycin, dilthiazem, amiodaron, verapamil,
fluconazole, ciclosporin, stiripentol, itraconazol, ketoconazol, voriconazol,
posaconazol, clarithromycin, ..), systemic use of fusidic acid
and ciclosporin.
- Any contra-indications to the use of statins.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2018-000647-89-NL |
| CCMO | NL65001.018.18 |