Recruiting
Early Phase 1

Observational Study

Sponsor:

National Institute of Neurological Disorders and Stroke (NINDS)

Code:

NCT06472622

Conditions

Fatigue Syndrome, Chronic

Eligibility Criteria

Sex: All

Age: 18 - 50

Healthy Volunteers: Not accepted

Interventions

Thermal Pain Stimulation

Physical Effort Stimulation

Study Details

Brief summary:

Background:

The way the brain processes rewards and punishments may play a role in some disorders of the nervous system. People with chronic overlapping pain conditions (such as myalgic encephalomyelitis/chronic fatigue syndrome \[ME/CFS\]) may have heightened responses to unpleasant, punishing sensations. Some of these conditions may also cause heightened responses to effort; this is an unpleasant sensation felt during physical and mental exertion.

Objective:

To learn more about how the brain processes different unpleasant sensations.

Eligibility:

People aged 18 to 50 years with ME/CFS. Healthy volunteers are also needed.

Design:

Participants will have 3 visits in 1 to 5 weeks.

Visit 1: Participants may have a neurologic exam. They will have a mock magnetic resonance imaging (MRI) scan. They will lie on a bed in a wooden tube while they practice 2 tasks:

Thermal pain rating: A device that creates mild to moderate heat will be placed on one leg.

Physical effort rating: Participants will squeeze a plastic bar with different levels of force.

Visit 2: Participants will have a real MRI scan. They will lie on a table that slides into a large tube.

Visit 3: Participants will have another MRI scan. They will repeat the thermal pain and physical effort tasks while in the scanner. Sensors will be placed on 1 arm to measure how the muscles function as they squeeze the bar.

Their heart rate will be tested: They will hold their finger against a camera lens for 1 minute. They will do 2 other tasks: 1 requires repeatedly pressing a key on a keyboard, and the other requires squeezing a bar.

Conditions

Fatigue Syndrome, Chronic

Study ID

NCT06472622

Start date

Apr 9, 2025

Status verified date

Sep 16, 2026

Completion date

Jun 30, 2034

Anticipated

Primary completion date

Jun 30, 2034

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 50

Healthy Volunteers: Not accepted

  • INCLUSION CRITERIA:

Healthy Controls: In order to be eligible to participate in this study as a healthy control, an individual must meet all the following criteria:

1. Ability of subject to understand and the willingness to sign a written informed consent document.
2. Stated willingness to comply with all study procedures and availability for the duration of the study.
3. Male or female, aged 18-50 (inclusive).
4. Good general health as evidenced by medical history and/or physical examination.

ME/CFS Patients: In order to be eligible to participate in this study as an ME/CFS patient, an individual must meet all the following criteria:

1. Ability of subject to understand and the willingness to sign a written informed consent document.
2. Stated willingness to comply with all study procedures and availability for the duration of the study.
3. Male or female, aged 18-50 (inclusive).
4. Has a diagnosis of ME/CFS, meeting at least one of three ME/CFS criteria: the 1994 Fukuda Criteria, the 2003 Canadian Consensus Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, or the Institute of Medicine Diagnostic Criteria.

EXCLUSION CRITERIA:

Healthy Controls:

1. Any current major neurological or psychiatric disorder such as (but not limited to) stroke, Parkinson s disease, Alzheimer s disease, schizophrenia, or major depressive disorder.
2. Any other current major medical disorder, such as a kidney disease, liver disease, cardiovascular disease, chronic pain condition, or any other disorder which, in the opinion of the PI would make participation risky for the individual or negatively affect the individual s ability to cooperate with study procedures.
3. Current use of medications acting primarily on the central nervous system, such as antidepressants, stimulants, etc.
4. Use of opioid medications for more than two weeks within the last two years or any use in the last month.
5. Current or history of substance use disorder, binge drinking, illegal drug use, or excessive tobacco use (defined as more than 10 cigarettes of nicotine per week).
6. Any more than occasional use of cannabis, defined as a score >1 (indicating use on more than one or two days in the last two weeks) on the marijuana use item of the DSM-5 Level 2-Substance Use-Adult questionnaire.
7. Any use of other illicit drugs or misuse of prescription medications, defined as a score >0 on any of the other items of the DSM-5 Level 2-Substance Use-Adult questionnaire.
8. Condition or injury affecting grip.
9. Condition or injury affecting extremities that would alter peripheral sensitivity to painful thermal stimuli or would otherwise cause such stimuli to be contraindicated.
10. Contraindications to MRI, including ferromagnetic metal in the cranial cavity or eye, implanted neural stimulator, cochlear implant, or ocular foreign body, implanted cardiac pacemaker, auto-defibrillator, or pump, non-removable body piercing, claustrophobia, inability to lie supine for 90 minutes, known pregnancy, or plans to become pregnant during the study.
11. Members of the NINDS BNU and their family members.
12. Non-English speakers will be excluded from the study as several study instruments do not have validated translations.

ME/CFS Patients:

1. Any current major neurological or psychiatric disorder, other than ME/CFS, such as (but not limited to) stroke, Parkinson s disease, Alzheimer s disease, schizophrenia, or major depressive disorder.
2. Any other current major medical disorder, other than ME/CFS, such as a kidney disease, liver disease, cardiovascular disease, chronic pain condition, or any other disorder which, in the opinion of the PI would make participation risky for the individual or negatively

affect the individual s ability to cooperate with study procedures.
3. Current use of psychomotor stimulants, antipsychotics, or benzodiazepines.
4. Use of opioid medications for more than two weeks within the last two years or any use in the last month.
5. Current or history of substance use disorder, binge drinking, illegal drug use, or excessive tobacco use (defined as more than 10 cigarettes of nicotine per week).
6. Any more than occasional use of cannabis, defined as a score >1 (indicating use on more than one or two days in the last two weeks) on the marijuana use item of the DSM-5 Level 2-Substance Use-Adult questionnaire.
7. Any use of other illicit drugs or misuse of prescription medications, defined as a score >0 on any of the other items of the DSM-5 Level 2-Substance Use-Adult questionnaire.
8. Condition or injury affecting grip.
9. Condition or injury affecting extremities that would alter peripheral sensitivity to painful thermal stimuli or would otherwise cause such stimuli to be contraindicated.
10. Contraindications to MRI, including ferromagnetic metal in the cranial cavity or eye, implanted neural stimulator, cochlear implant, or ocular foreign body, implanted cardiac pacemaker, auto-defibrillator, or pump, non-removable body piercing, claustrophobia, inability to lie supine for 90 minutes, known pregnancy, or plans to become pregnant during the study.
11. Members of the NINDS BNU and their family members.
12. Non-English speakers will be excluded from the study as several study instruments do not have validated translations.

Study Design

Enrollment

47 participants

Anticipated

Intervention Model

Single group

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

other: Single Arm

This is a single-arm study. The order of intervention administration will be counterbalanced within this single arm.

Interventions

Thermal Pain Stimulation

Thermal pain will be administered during fMRI neuroimaging via a thermal stimulation device (Medoc Ltd., Advanced Medical System, Israel; 510K: K052357; K041908; K922052) to examine brain activity corresponding to the experience of this stimulus. This device and associated system carries an FDA 510 (K) clearance.

Physical Effort Stimulation

Physical effort will be administered during fMRI neuroimaging via a hand dynamometer attachment for a physiological monitoring system (BIOPAC Systems, Inc., Goleta, CA, USA) to examine brain activity corresponding to the experience of this stimulus. This device has not received pre-marked approval or 510 (K) clearance by the FDA.

Primary outcome measure

  • Determine which regions of the SVN are specifically involved in the subjective experience of unpleasantness associated with sensations of pain. [ Time Frame: The measurement will be assessed concurrently with thermal pain stimulus administration during the fMRI procedure associated with one of the study visits, 1-31 days following the visit for the first session. ]
  • Determine which regions of the SVN are specifically involved in the subjective experience of unpleasantness associated with sensations of physical effort. [ Time Frame: The measurement will be assessed concurrently with physical effort stimulus administration during the fMRI associated with one of the study visits, 1-31 days following the visit for the first session. ]

Central Contacts and Locations

Central contacts

Locations

National Institutes of Health Clinical Center

Recruiting

Bethesda, Maryland, United States, 20892

Contacts

More Information

Sponsor

National Institute of Neurological Disorders and Stroke (NINDS)

Last update posted

Sep 18, 2026

Last verified

Sep 16, 2026

Keywords

  • Punishment
  • Fatigue Syndrome, Chronic
  • Pain
  • Physical Exertion
  • Effort
  • Brain
  • Magnetic Resonance Imaging
  • Neuroimaging
  • Psychophysics
  • Reward

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-09. This information was provided to ClinicalTrials.gov by National Institute of Neurological Disorders and Stroke (NINDS) on 2026-09-18. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.