To explore, whether markers of mitochondrial dysfunction measured in isolated PBMCs or immune cell subpopulations differ between subjects with mitochondrial disorders and cardiomyopathy and healthy volunteers.
ID
Source
Brief title
Condition
- Heart failures
- Metabolic and nutritional disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The difference in performance of mitochondrial function assays between MitoD
subjects and HV subjects
Secondary outcome
Difference in blood serum/plasma markers associated with inflammation and
oxidative stress (IL-6, hs-CRP, PTX-3, and GDF-15) between MitoD subjects and
HV subjects
Background summary
OMT-28 is a fully synthetic small molecule that belongs to the family of
17,18-epoxyeicosatetraenoic acid (17,18-EEQ) analogs, a natural metabolite of
the omega-3 fatty acid eicosapentaenoic acid (EPA).1,2 The safety of various
doses of OMT-28 was studied in toxicology studies in various species, as well
as in a First-in-Human study including a Single-Ascending-Dose (SAD) and
Multiple-Ascending-Dose (MAD) part, and a Phase 2a Proof-of-Concept (PoC) study
(PROMISE-AF) in subjects with atrial fibrillation.3 Recent non-clinical studies
showed the potential of OMT-28 to positively affect mitochondrial function and
survival. Therefore, OMT-28 is currently being developed for the treatment of
cardiomyopathy in subjects with mitochondrial diseases and in subjects with
coronary artery disease.
Subjects with mitochondrial disorder and cardiomyopathy might benefit from
treatment with OMT-28, due to the potential positive effects of OMT-28 on
mitochondrial function and survival.4,5 This non-interventional study aims to
characterize these subjects using different markers of mitochondrial function
and inflammation, and to assess using ex-vivo assays in blood the potential
effect of OMT-28 on mitochondrial function.
The aim of this non-interventional study is to characterize subjects regarding
their levels of mitochondrial dysfunction and inflammation markers, and to
identify those subjects who might benefit most from OMT-28 treatment based on
the ex-vivo blood assay results. The results of this study are supposed to
guide the design of future clinical interventional studies with OMT-28.
Study objective
To explore, whether markers of mitochondrial dysfunction measured in isolated
PBMCs or immune cell subpopulations differ between subjects with mitochondrial
disorders and cardiomyopathy and healthy volunteers.
Study design
This is a non-interventional study with a cross-sectional design. Subjects will
not be exposed to treatment.
Study burden and risks
Neither MitoD patients nor HVs will directly benefit from this study. MitoD
patients might benefit indirectly, as OMT-28 is evaluated as a potential
treatment for MitoD. As all study assessments are considered minimally
invasive, the benefit-risk evaluation is considered acceptable for the
participants. This is an exploratory, non-interventional study to characterize
the markers of mitochondrial dysfunction, inflammation and cardiac dysfunction
in MitoD subjects and healthy volunteers. The distribution and variability of
these biomarkers are unknown in these populations
*
Robert-Rössle-Strasse 10
Berlin 13125
DE
Robert-Rössle-Strasse 10
Berlin 13125
DE
Listed location countries
Age
Inclusion criteria
All subjects
1. Adults between 18 and 75 years, inclusive at screening
2. Body mass index (BMI) 18.0 to 30.0 kg/m2, inclusive at screening
3. Ability and willingness to abstain from alcohol at study visit
4. Subject (and/or parent/legal guardian) has voluntarily signed consent form.
5. Willingness and ability to comply with all study procedures.
6. Ability to communicate with the investigator in Dutch or English
Subjects of cohort 1 with Mitochondrial Disorder (in addition)
7. Diagnosis of Mitochondrial Disorder, confirmed by:
a. Genetic testing at any time prior to screening showing m.3243A>G mutation
b. Newcastle Mitochondrial Disease Scale (NMDAS) score *11
8. Any current cardiomyopathy (e.g., LVH, reduced systolic function or strain,
ECG abnormalities consistent with cardiac involvement etc.).
Subjects of cohort 2 Healthy Volunteers (in addition)
9. Judged to be in good health in the opinion of the Investigator on the basis
of a medical evaluation that reveals the absence of any clinically relevant
abnormality
10. Matching to MitoD group for age (+/- 5 years), gender, and BMI (+/- 3
kg/m2).
Exclusion criteria
2. Women with positive urine hCG test at screening
3. Subject has a hemoglobin values outside the normal limits (as per local lab)
4. Subject has received drug therapy with any cytostatic, sGC
stimulator/activator or nitrate agent during the last 3 months
5. Subjects with severe aortic valve stenosis
6. Subject has received drug therapy with Metformin during last 3 months
7. Significant psychiatric or neurological disorder that would inhibit the
subject from being compliant with study procedures
15. Positive nasopharyngeal rapid antigen test for SARS-CoV-2 at admission to
the clinical research center
16. Subject has received any vaccination in the last 2 weeks prior to Visit 1
Subjects of cohort 2 Healthy Volunteers (in addition)
17. Subject has acute decompensated hepatic, gastrointestinal, respiratory,
cardiovascular, metabolic, immunological, or hormonal disorders.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL77982.056.21 |