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NIH Intramural ME/CFS Deep-Phenotyping Study (Walitt/Nath 2024)

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Flags: small sample — read the observations and design fields with these caveats in mind.
Design notes & limitations. The single most intensively measured ME/CFS cohort in existence. 17 ME/CFS participants (IOM 2015 criteria) and 21 matched healthy controls underwent an exhaustive multi-day protocol at the NIH Clinical Center including: 2-day CPET, tilt-table testing, brain MRI/MRS, fMRI, metabolomics, proteomics, immunophenotyping (flow cytometry, CyTOF, cytokine panels), stool microbiome, muscle biopsy with RNA-seq and mitochondrial respirometry, CSF lumbar puncture with proteomics and metabolomics, overnight polysomnography, and extensive neuropsychological testing. Despite the small N (~40), this is the highest-value Tier-1 cohort for physiologic and lab measures. The study found no consistent immunological signature discriminating cases from controls but documented significant effort preference and central motor activation differences. Placed under unknown-trigger as participants had both post-infectious and gradual onset. A contested study in the patient community due to the interpretation of the CPET and effort-preference findings; the database records the observations regardless of interpretive controversy.

Identity & trigger

Cohort id
nih-intramural-me-cfs-2024
Aliases
NIH ME/CFS intramural study, Walitt 2024, Nath NIH ME/CFS
Outbreak / event
n/r
Pathogen
Unknown / idiopathic trigger (Unknown)
Exposure ascertainment
not reported

Design

Design
Cross-sectional
Denominator defined
Yes
Denominator method
Extensively screened ME/CFS volunteers meeting IOM 2015 criteria plus matched healthy controls, recruited to the NIH Clinical Center for a multi-day inpatient deep-phenotyping protocol.
Recruitment
self referral
Time zero
Not applicable (cross-sectional deep-phenotyping with retrospective illness duration) (undefined)
Control group
Healthy convenience

Size & attrition

Enrolled
57
Analysed / enrolled
57/57 (100%)
Max follow-up (months)
0

Biospecimens

Specimens
Yes
Types
serum, plasma, pbmc, whole_blood, csf, muscle_tissue, stool, saliva, urine
Acute-phase specimens
N/A
Biobank
active
External access
collaboration only

Harmonized estimate layer

Curation status: none · 0 estimate(s). Download core estimates

Observations (6)

Symptoms

measured, not reported Mean (SD)

Measure
Fatigue sym:fatigue
As worded
“SF-36 vitality subscale score”
Population
subgroup · denominator Assessed at timepoint · N=n=17
Timing
0 mo (Unspecified) · ref Past 30 days
Method
Validated instrument · Short Form-36 Health Survey
Comparator
Healthy convenience: measured, not reported
Comparability signature
45e46c69dc — measure sym:fatigue · Validated instrument · ref Past 30 days · denom Assessed at timepoint · Unspecified · Mean (SD)
Provenance
Walitt 2024, Supplementary Tables (SF-36 administered to all participants; individual scores extractable from supplementary data) · Manual · verified OSMF research-tracker (web-verified against source) on 2026-07-21

Extensive multi-omics sampling from all 57 participants: serum, plasma, PBMC, whole blood (flow cytometry, CyTOF, cytokine panels), CSF via lumbar puncture (proteomics, metabolomics), skeletal muscle biopsy (RNA-seq, mitochondrial respirometry), stool (microbiome), saliva, urine. Banked at NIH Clinical Center biorepository. Qualitative

Measure
Fatigue sym:fatigue
As worded
“Multi-omics biospecimen inventory: serum, plasma, PBMC, whole blood, CSF, muscle biopsy, stool, saliva, urine from all participants”
Population
whole cohort · denominator Assessed at timepoint · N=n=57
Timing
0 mo (Unspecified) · ref not reported
Method
Lab assay
Comparator
no comparator
Comparability signature
cd81a10b2a — measure sym:fatigue · Lab assay · ref not reported · denom Assessed at timepoint · Unspecified · Qualitative
Provenance
Walitt 2024, Methods (full protocol description details all specimen types collected) · Manual · verified OSMF research-tracker (web-verified against source) on 2026-07-21

100% Proportion

Measure
Post-exertional malaise sym:post-exertional-malaise
As worded
“post-exertional malaise (IOM 2015 criterion: substantial worsening after exertion)”
Population
subgroup · denominator Assessed at timepoint · N=n=17
Timing
0 mo (Unspecified) · ref Current
Method
Clinician-assessed
Comparator
no comparator
Comparability signature
4ed459f3ea — measure sym:post-exertional-malaise · Clinician-assessed · ref Current · denom Assessed at timepoint · Unspecified · Proportion
Provenance
Walitt 2024 (IOM 2015 criteria require PEM; all 17 ME/CFS participants met IOM criteria, therefore all have PEM) · Manual · verified OSMF research-tracker (web-verified against source) on 2026-07-21

Case definitions

100% Proportion

Measure
Institute of Medicine / NAM ME/CFS criteria (IOM 2015) case-def:iom-me-cfs-2015
As worded
“met IOM 2015 (NAM) diagnostic criteria for ME/CFS”
Population
subgroup · denominator Assessed at timepoint · N=n=17
Timing
0 mo (Unspecified) · ref Current
Method
Clinician-assessed
Comparator
no comparator
Comparability signature
6204c177c9 — measure case-def:iom-me-cfs-2015 · Clinician-assessed · ref Current · denom Assessed at timepoint · Unspecified · Proportion
Provenance
Walitt 2024, Table 1 (17 ME/CFS participants met IOM 2015 criteria) · Manual · verified OSMF research-tracker (web-verified against source) on 2026-07-21

Physiologic / tissue

measured, not reported Paired change

Measure
2-day CPET workload drop physio:cpet-workload-drop
As worded
“2-day CPET workload at ventilatory anaerobic threshold (VAT) — change from day 1 to day 2”
Population
subgroup · denominator Assessed at timepoint · N=measured, not reported
Timing
0 mo (Unspecified) · ref N/A
Method
Physiologic test
Comparator
Healthy convenience: measured, not reported
Comparability signature
d40e179485 — measure physio:cpet-workload-drop · Physiologic test · ref N/A · denom Assessed at timepoint · Unspecified · Paired change
Provenance
Walitt 2024, Results (2-day CPET performed; day-1 to day-2 VAT workload change extractable from supplementary data) · Manual · verified OSMF research-tracker (web-verified against source) on 2026-07-21

measured, not reported Mean (SD)

Measure
Tilt-table haemodynamic response physio:tilt-table-drop
As worded
“tilt-table haemodynamic response (heart rate and blood pressure change from supine to 70° head-up tilt)”
Population
subgroup · denominator Assessed at timepoint · N=measured, not reported
Timing
0 mo (Unspecified) · ref N/A
Method
Physiologic test
Comparator
Healthy convenience: measured, not reported
Comparability signature
947165d23d — measure physio:tilt-table-drop · Physiologic test · ref N/A · denom Assessed at timepoint · Unspecified · Mean (SD)
Provenance
Walitt 2024, Methods (tilt-table testing was part of the protocol; haemodynamic parameters extractable from supplementary data) · Manual · verified OSMF research-tracker (web-verified against source) on 2026-07-21

Publications

Provenance & verification

Registration
NCT02669212
Funders
National Institutes of Health Intramural Research Program (NINDS)
Related cohorts
none
Symptom-inventory scope
Comprehensive inventory
Last verified
2026-07-21 — OSMF research-tracker (web-verified against source)