{
  "schema_version": "2.0.0",
  "id": "nih-intramural-me-cfs-2024",
  "name": "NIH Intramural ME/CFS Deep-Phenotyping Study (Walitt/Nath 2024)",
  "aliases": [
    "NIH ME/CFS intramural study",
    "Walitt 2024",
    "Nath NIH ME/CFS"
  ],
  "outbreak_event": null,
  "pathogen_id": "unknown-trigger",
  "pathogen_class": "unknown",
  "exposure_ascertainment": "not_reported",
  "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_source": "self_referral",
  "time_zero_definition": "Not applicable (cross-sectional deep-phenotyping with retrospective illness duration)",
  "time_zero_precision": "undefined",
  "control_group": "healthy_convenience",
  "control_matching_variables": ["age", "sex", "bmi"],
  "n_source_population": null,
  "n_enrolled": 57,
  "n_analysed": 57,
  "followups": [
    {
      "months": 0,
      "n_assessed": 57,
      "n_lost": null
    }
  ],
  "max_followup_months": 0,
  "instruments": [
    "sf-36",
    "promis-fatigue",
    "compass-31"
  ],
  "case_definition": "iom_nam_2015",
  "pem_assessed": "yes_single_item",
  "objective_measures": [
    "cpet_two_day",
    "tilt_table",
    "imaging",
    "lab_panel",
    "muscle_biopsy",
    "other_biopsy",
    "polysomnography"
  ],
  "specimens_collected": true,
  "specimen_types": [
    "serum",
    "plasma",
    "pbmc",
    "whole_blood",
    "csf",
    "muscle_tissue",
    "stool",
    "saliva",
    "urine"
  ],
  "acute_phase_specimens": "not_applicable",
  "storage": "NIH Clinical Center −80 °C biorepository",
  "biobank_status": "active",
  "consent_future_use": "broad",
  "external_access": "collaboration_only",
  "contact": "Avindra Nath / Brian Walitt, NIH NINDS",
  "registration_id": "NCT02669212",
  "funders": [
    "National Institutes of Health Intramural Research Program (NINDS)"
  ],
  "conflicts": null,
  "data_availability": "Individual-level data available via NIH data-sharing policies",
  "notes": "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.",
  "publications": [
    {
      "id": "walitt-2024-nih-me-cfs",
      "title": "Deep phenotyping of post-infectious myalgic encephalomyelitis/chronic fatigue syndrome",
      "authors": "Walitt B, Singh K, LaMunion SR, et al.",
      "year": 2024,
      "journal": "Nature Communications",
      "doi": "10.1038/s41467-024-45107-3",
      "pmid": "38358935",
      "url": "https://pubmed.ncbi.nlm.nih.gov/38358935/",
      "open_access": true,
      "is_primary_cohort_paper": true
    }
  ],
  "symptom_inventory_scope": "comprehensive_inventory",
  "n_symptoms_queried": null,
  "symptom_instrument_note": "Extensive battery: SF-36, PROMIS fatigue, COMPASS-31, McGill Pain Questionnaire, Multidimensional Fatigue Inventory (MFI-20), neuropsychological test battery, structured clinical history",
  "related_cohorts": [],
  "last_verified": "2026-07-21",
  "verified_by": "OSMF research-tracker (web-verified against source)",
  "harmonisation_ruleset": "pais-harmony-v1",
  "flags": ["small_sample"],
  "observations": [
    {
      "id": "nihmecfs-2024-caseness",
      "cohort_id": "nih-intramural-me-cfs-2024",
      "publication_id": "walitt-2024-nih-me-cfs",
      "schema_version": "2.0.0",
      "measure_id": "case-def:iom-me-cfs-2015",
      "measure_verbatim": "met IOM 2015 (NAM) diagnostic criteria for ME/CFS",
      "population": {
        "scope": "subgroup",
        "stratum": { "variable": "case_status", "level": "ME/CFS" },
        "denominator_basis": "assessed_at_timepoint",
        "n_assessed": 17
      },
      "timing": {
        "timepoint_months": 0,
        "timepoint_band": "unspecified",
        "reference_period": "current",
        "is_cumulative": false
      },
      "method": {
        "ascertainment": "clinician_assessed",
        "instrument_id": null,
        "severity_threshold": null,
        "blinded_assessment": "not_reported"
      },
      "value": {
        "type": "proportion",
        "numerator": 17,
        "denominator": 17,
        "percent": 100,
        "ci": null,
        "precision": "exact"
      },
      "comparator": {
        "group": "none",
        "value": { "status": "not_applicable" },
        "effect": null
      },
      "harmonised": null,
      "provenance": {
        "source_locator": "Walitt 2024, Table 1 (17 ME/CFS participants met IOM 2015 criteria)",
        "extracted_by": null,
        "extracted_on": null,
        "verified_by": "OSMF research-tracker (web-verified against source)",
        "verified_on": "2026-07-21",
        "extraction_method": "manual"
      }
    },
    {
      "id": "nihmecfs-2024-fatigue-sf36-vt",
      "cohort_id": "nih-intramural-me-cfs-2024",
      "publication_id": "walitt-2024-nih-me-cfs",
      "schema_version": "2.0.0",
      "measure_id": "sym:fatigue",
      "measure_verbatim": "SF-36 vitality subscale score",
      "population": {
        "scope": "subgroup",
        "stratum": { "variable": "case_status", "level": "ME/CFS" },
        "denominator_basis": "assessed_at_timepoint",
        "n_assessed": 17
      },
      "timing": {
        "timepoint_months": 0,
        "timepoint_band": "unspecified",
        "reference_period": "past_30d",
        "is_cumulative": false
      },
      "method": {
        "ascertainment": "validated_instrument_threshold",
        "instrument_id": "sf-36",
        "severity_threshold": null,
        "blinded_assessment": "not_reported"
      },
      "value": {
        "type": "mean_sd",
        "mean": { "status": "measured_not_reported" },
        "sd": { "status": "measured_not_reported" },
        "n": 17,
        "ci": null
      },
      "comparator": {
        "group": "healthy_convenience",
        "value": { "status": "measured_not_reported" },
        "effect": null
      },
      "harmonised": null,
      "provenance": {
        "source_locator": "Walitt 2024, Supplementary Tables (SF-36 administered to all participants; individual scores extractable from supplementary data)",
        "extracted_by": null,
        "extracted_on": null,
        "verified_by": "OSMF research-tracker (web-verified against source)",
        "verified_on": "2026-07-21",
        "extraction_method": "manual"
      }
    },
    {
      "id": "nihmecfs-2024-pem-cpet",
      "cohort_id": "nih-intramural-me-cfs-2024",
      "publication_id": "walitt-2024-nih-me-cfs",
      "schema_version": "2.0.0",
      "measure_id": "physio:cpet-workload-drop",
      "measure_verbatim": "2-day CPET workload at ventilatory anaerobic threshold (VAT) — change from day 1 to day 2",
      "population": {
        "scope": "subgroup",
        "stratum": { "variable": "case_status", "level": "ME/CFS" },
        "denominator_basis": "assessed_at_timepoint",
        "n_assessed": { "status": "measured_not_reported" }
      },
      "timing": {
        "timepoint_months": 0,
        "timepoint_band": "unspecified",
        "reference_period": "not_applicable",
        "is_cumulative": false
      },
      "method": {
        "ascertainment": "physiologic_test",
        "instrument_id": null,
        "severity_threshold": null,
        "blinded_assessment": "not_reported"
      },
      "value": {
        "type": "paired_change",
        "baseline": { "status": "measured_not_reported" },
        "followup": { "status": "measured_not_reported" },
        "delta": { "status": "measured_not_reported" },
        "sd_delta": { "status": "measured_not_reported" },
        "n_pairs": { "status": "measured_not_reported" },
        "p_value": null
      },
      "comparator": {
        "group": "healthy_convenience",
        "value": { "status": "measured_not_reported" },
        "effect": null
      },
      "harmonised": null,
      "provenance": {
        "source_locator": "Walitt 2024, Results (2-day CPET performed; day-1 to day-2 VAT workload change extractable from supplementary data)",
        "extracted_by": null,
        "extracted_on": null,
        "verified_by": "OSMF research-tracker (web-verified against source)",
        "verified_on": "2026-07-21",
        "extraction_method": "manual"
      }
    },
    {
      "id": "nihmecfs-2024-tilt-table",
      "cohort_id": "nih-intramural-me-cfs-2024",
      "publication_id": "walitt-2024-nih-me-cfs",
      "schema_version": "2.0.0",
      "measure_id": "physio:tilt-table-drop",
      "measure_verbatim": "tilt-table haemodynamic response (heart rate and blood pressure change from supine to 70° head-up tilt)",
      "population": {
        "scope": "subgroup",
        "stratum": { "variable": "case_status", "level": "ME/CFS" },
        "denominator_basis": "assessed_at_timepoint",
        "n_assessed": { "status": "measured_not_reported" }
      },
      "timing": {
        "timepoint_months": 0,
        "timepoint_band": "unspecified",
        "reference_period": "not_applicable",
        "is_cumulative": false
      },
      "method": {
        "ascertainment": "physiologic_test",
        "instrument_id": null,
        "severity_threshold": null,
        "blinded_assessment": "not_reported"
      },
      "value": {
        "type": "mean_sd",
        "mean": { "status": "measured_not_reported" },
        "sd": { "status": "measured_not_reported" },
        "n": { "status": "measured_not_reported" },
        "ci": null
      },
      "comparator": {
        "group": "healthy_convenience",
        "value": { "status": "measured_not_reported" },
        "effect": null
      },
      "harmonised": null,
      "provenance": {
        "source_locator": "Walitt 2024, Methods (tilt-table testing was part of the protocol; haemodynamic parameters extractable from supplementary data)",
        "extracted_by": null,
        "extracted_on": null,
        "verified_by": "OSMF research-tracker (web-verified against source)",
        "verified_on": "2026-07-21",
        "extraction_method": "manual"
      }
    },
    {
      "id": "nihmecfs-2024-specimens-banked",
      "cohort_id": "nih-intramural-me-cfs-2024",
      "publication_id": "walitt-2024-nih-me-cfs",
      "schema_version": "2.0.0",
      "measure_id": "sym:fatigue",
      "measure_verbatim": "Multi-omics biospecimen inventory: serum, plasma, PBMC, whole blood, CSF, muscle biopsy, stool, saliva, urine from all participants",
      "population": {
        "scope": "whole_cohort",
        "stratum": null,
        "denominator_basis": "assessed_at_timepoint",
        "n_assessed": 57
      },
      "timing": {
        "timepoint_months": 0,
        "timepoint_band": "unspecified",
        "reference_period": "not_reported",
        "is_cumulative": false
      },
      "method": {
        "ascertainment": "lab_assay",
        "instrument_id": null,
        "severity_threshold": null,
        "blinded_assessment": "not_applicable"
      },
      "value": {
        "type": "qualitative",
        "text": "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.",
        "n_supporting": 57
      },
      "comparator": {
        "group": "none",
        "value": { "status": "not_applicable" },
        "effect": null
      },
      "harmonised": null,
      "provenance": {
        "source_locator": "Walitt 2024, Methods (full protocol description details all specimen types collected)",
        "extracted_by": null,
        "extracted_on": null,
        "verified_by": "OSMF research-tracker (web-verified against source)",
        "verified_on": "2026-07-21",
        "extraction_method": "manual"
      }
    },
    {
      "id": "nihmecfs-2024-pem-proportion",
      "cohort_id": "nih-intramural-me-cfs-2024",
      "publication_id": "walitt-2024-nih-me-cfs",
      "schema_version": "2.0.0",
      "measure_id": "sym:post-exertional-malaise",
      "measure_verbatim": "post-exertional malaise (IOM 2015 criterion: substantial worsening after exertion)",
      "population": {
        "scope": "subgroup",
        "stratum": { "variable": "case_status", "level": "ME/CFS" },
        "denominator_basis": "assessed_at_timepoint",
        "n_assessed": 17
      },
      "timing": {
        "timepoint_months": 0,
        "timepoint_band": "unspecified",
        "reference_period": "current",
        "is_cumulative": false
      },
      "method": {
        "ascertainment": "clinician_assessed",
        "instrument_id": null,
        "severity_threshold": null,
        "blinded_assessment": "not_reported"
      },
      "value": {
        "type": "proportion",
        "numerator": 17,
        "denominator": 17,
        "percent": 100,
        "ci": null,
        "precision": "exact"
      },
      "comparator": {
        "group": "none",
        "value": { "status": "not_applicable" },
        "effect": null
      },
      "harmonised": null,
      "provenance": {
        "source_locator": "Walitt 2024 (IOM 2015 criteria require PEM; all 17 ME/CFS participants met IOM criteria, therefore all have PEM)",
        "extracted_by": null,
        "extracted_on": null,
        "verified_by": "OSMF research-tracker (web-verified against source)",
        "verified_on": "2026-07-21",
        "extraction_method": "manual"
      }
    }
  ],
  "estimates_status": "none"
}