The aim of this study is to quantify neuroinflammation and whole-body inflammation with [18F]DPA-714 PET scans in post-COVID-19 patients and relate it to cognitive, psychiatric and post-infectious fatigue symptoms.
ID
Source
Brief title
Condition
- Central nervous system infections and inflammations
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary parameter is the measurement of neuro-inflammation in vivo with the
[18F]DPA-714 (±286MBq, 4,9mSv) 70 minutes PET scan, alternately capturing brain
(60 minutes) and body (10 minutes; pelvic to head) with both continuous on-line
and manual arterial blood sampling for full quantification ([18F]DPA-714
volume of distribution).15,16. Brain MRI will be performed for functional and
anatomical information.
Secondary outcome
Secondary parameters include whole-body inflammation as measured with 60-70 min
body PET. In adddition, we will use CIS, BDI, GAD7 and neuropsychological
evaluation to assess chronic fatigue, depressive, anxiety and cognitive
symptoms, partially for descriptive purposes. In addition, questionnaires to
evaluate smell and taste complaints will be evaluated.
Background summary
The scale of the current COVID-19 pandemic is unprecedented with >500000
infections to date in the Netherlands and >54 million globally
(https://COVID19.who.int). Already a great number of post-COVID-19 patients
have developed *chronic* complaints, such as fatigue and cognitive complaints,
which persists >2months after infection (36-53%).1,2 Post-infectious fatigue
(PIF) is a condition characterized by chronic, debilitating, and unexplained
fatigue3, months after an infection.45-7 There is evidence that peripheral8-12
and neuroinflammation13,14 are involved in post-infectious fatigue and
cognitive complaints, but precise pathophysiological mechanisms and causal
relationship with viral infections are still unknown.
Study objective
The aim of this study is to quantify neuroinflammation and whole-body
inflammation with [18F]DPA-714 PET scans in post-COVID-19 patients and relate
it to cognitive, psychiatric and post-infectious fatigue symptoms.
Study design
Cross-sectional observational case-control study
Study burden and risks
[18F]DPA-714 is a tracer with excellent in vivo stability and biodistribution.
It has been used as a tracer in animal and human studies in multiple
neurological diseases, including multiple sclerosis (MS), Alzheimer*s disease
(AD) and post-stroke, all of which did not identify AEs or SAEs. Furthermore,
[18F]DPA-714 gives relatively minor radiation exposure, similar to other
fluorine-labeled tracers, within guidelines for radiation exposure for healthy
controls. Finally, withdrawal of arterial blood poses a very minor risk of
complications, such as infection at the injection site. There is no increased
risk associated with any of the other examinations performed
(neuropsychological or psychiatric evaluation or MRI), but these may be
experienced as burdensome by certain individuals. No patient-specific benefits
are expected. We expect TSPO specific binding to be increased in COVID-19
patients as compared to controls and post-COVID-19 individuals without chronic
fatigue or cognitive complaints.
De Boelelaan 1117
Amsterdam 1081HV
NL
De Boelelaan 1117
Amsterdam 1081HV
NL
Listed location countries
Age
Inclusion criteria
Group 1. In order to participate in this study, individuals with a previous
COVID-19 infection and with post-infectious fatigue or cognitive complaints
should meet the following criteria:
1) The patient was diagnosed with symptomatic COVID-19, confirmed by a positive
PCR for SARS-CoV-2, positive SARS-CoV-2 serology or CO-RADS (COVID-19 Reporting
and Data System) 4 or 5 on CT-scan, or antigen quicktest, or had typical
symptoms and was part of a household in which another person was tested
positive by PCR 2 weeks before or after the first day of illness;
2) The patient is 3 months after being diagnosed with COVID-19 or after
hospital discharge in case the patient was admitted.
3) The patient experiences severe levels of fatigue (>= 40) on the fatigue
subscale of the Checklist Individual Strength [CIS-fatigue]) and/or cognitive
complaints (>= 15) on the concentration subscale of the Checklist Individual
Strength [CIS-concentration]. The severe fatigue or cognitive complaints
started with or increased substantially directly after the onset of symptoms of
COVID-19
4) The patient reports physical/social disability (<= 65 on the Rand36 physical
functioning subscale or a score of >= 10 on the Work and Social Adjustment
Scale [WSAS]10;
5) The patient is in the range 30-65 years of age (to ensure radiation safety)
6) The patient has sufficient command of the Dutch language
7) Genotyping of rs6971 must show that patient is a mixed or high affinity
binder
Group 2. In order to participate in this study, individuals with a previous
COVID-19 infection and without post-infectious fatigue or cognitive complaints
should meet the following criteria:
1) The patient was diagnosed with symptomatic COVID-19, confirmed by a positive
PCR for SARS-CoV-2, positive SARS-CoV-2 serology or CO-RADS 4 or 5 on CT-scan,
or antigen quicktest, or had typical symptoms and was part of a household in
which another person was tested positive by PCR 2 weeks before or after the
first day of illness;
2) The patient is 3 months after being diagnosed with COVID-19 or after
hospital discharge in case the patient was admitted.
3) The patient experiences no significant levels of fatigue (< 35 on the
fatigue subscale of the Checklist Individual Strength [CIS-fatigue]) or
cognitive complaints (<15 on the concentration subscale of the Checklist
Individual Strength [CIS-concentration]) and does not subjectively major
symptoms of fatigue. or cognitive complaints. Based upon average of normal
population +1SD
4) The patient reports no physical/social disability (> 65 on the Rand36
physical functioning subscale or a score of < 10 on the Work and Social
Adjustment Scale [WSAS]10;
5) The patient is in the range 30-65 years of age (to ensure radiation safety)
6) The patient has sufficient command of the Dutch language
7) Genotyping of rs6971 must show that patient is a mixed or high affinity
binder
Group 3. Healthy controls should meet the following criteria:
1) Should be negatively tested for COVID-19 trough PCR, serology, antibodies,
or via antigen quicktest
2) No evidence for substantial fatigue or cognitive complaints as evidenced by
the CIS subscale fatigue (<35) and CIS subscale concentration (<15) and does
not subjectively major symptoms of fatigue or cognitive complaints. Based upon
average of normal population +1SD
3) The patient is in the range 30-65 years of age (to ensure radiation safety)
4) The patient has sufficient command of the Dutch language
5) Genotyping of rs6971 must show that patient is a mixed or high affinity
binder
Exclusion criteria
1) Rs6971 shows low affinity binding
2) Patients who are unable to lay still for scanning due to claustrophobia or
severe back pain or trypanophobia (fear of needles)
3) Gross neurological pathology (strategic or lobar infarcts) on MRI or CT that
may interfere with the interpretation of the PET scan.
4) Post-infectious complaints before COVID-19 or any other current disease of
infection that is known to cause substantial fatigue
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 | EUCTR2021-000781-15-NL |
| CCMO | NL77033.029.21 |