NIH Investigative Deep Phenotyping Study of Gulf War Veteran Health (Project NIH IN-DEPTH)

  • STATUS
    Recruiting
  • End date
    Dec 31, 2024
  • participants needed
    85
  • sponsor
    National Institute of Neurological Disorders and Stroke (NINDS)
Updated on 16 September 2022
Accepts healthy volunteers

Summary

Background

Gulf War illness (GWI) affects up to 210,000 U.S. veterans who served in the Middle East during the Gulf War in 1990-1991. Symptoms include fatigue, muscle and joint pain, forgetfulness, headaches, rashes, and sleep disturbances. Routine exams cannot determine the cause of GWI. Researchers need more information to understand this disease.

Objective

This natural history study will look for differences in Gulf War veterans who experienced GWI and those who did not.

Eligibility

Gulf War veterans with GWI. Healthy Gulf War veterans who do not have GWI are also needed.

Design

Participants will stay in the NIH Clinical Center as an inpatient for 2 weeks. They will undergo many tests.

Blood will be drawn many times throughout the study. Participants will also give urine, saliva, and stool samples.

Scans to measure the brain, leg muscles, bone density and body mass will be done.

They will have an exercise stress test and muscle strength tests.

Participants will sleep in a specialized room that measures the amount of oxygen they use and the carbon dioxide they produce on four consecutive nights.

A sample of fluid will be collected from inside the spine.

Participants will take many surveys. Some will ask about their activities. Some will be about emotional and mental health. Some will be about thinking, memory, and behavior.

Optional tests include other imaging scans. Samples of skin and muscle may be taken.

After discharge, participants will wear activity monitors for 14 days. They will keep a diary of their symptoms, including fatigue, pain, and sleep, while wearing the monitors....

Description

Study Description:

This protocol is part of a joint collaboration with the Veterans Administration (VA) known as (Project IN-DEPTH). The Veterans Administration protocol will recruit and identify participants for the NIH study, and maintain a repository of samples through a VA protocol (VA IN-DEPTH). The NIH protocol (NIH IN-DEPTH) will conduct deep phenotyping evaluations on study participants.

Gulf War Illness (GWI) and Gulf War Chronic Multi-Symptom Illness are names that have been used to describe a disorder of fatigue, muscle and joint pain, loss of concentration, forgetfulness, headache, respiratory complaints, rashes, sleep disturbances, and/or gastrointestinal distress. The purpose of this study is to learn more about GWI from veterans deployed in Persian Gulf during the first Gulf War.

In this study, two groups of veterans who were deployed to the Persian Gulf war between August 1990 and June 1991 will be enrolled, those who are healthy veteran soldiers (HVS) and those with GWI. Participants will have an inpatient study visit typically lasting 14 days to explore clinical and biological phenotypes through evaluations via questionnaires, medical procedures such as exercise testing, history and physical examination, and laboratory evaluation of samples.

This protocol is a sister study to the NIH protocol 16-N-0058: Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS) at NIH. The symptoms of GWI and ME/CFS are very similar and much may be learned about each disorder through comparison. For this reason, the two studies will use similar methods. Participants in 16- N-0058 had previously consented to sharing of data, therefore datasets from this NIH IN-DEPTH protocol and 16-N-0058 will be shared and combined to perform several of the planned exploratory analyses.

This study will take place at the National Institutes of Health (NIH) Clinical Center in Bethesda, Maryland.

Objectives
  • Primary Objective:

--To explore the clinical and biological phenotypes of veterans with GWI and healthy veteran soldiers (HVS).

  • Secondary Objectives:
  • To explore the pathophysiology of fatigue and GWI symptom flares. Fatigue will be explored using tasks designed to create muscular and cognitive fatigue. GWI symptom flares will be explored using an exercise stress test and measuring the symptomatic and biological changes.

To compare the clinical and biological phenotypes between GWI, HVS, ME/CFS, and healthy volunteers.

Endpoints

-Outcome measures

--The primary purpose of this protocol is to perform exploratory analysis of collected data and samples for the generation of new hypotheses regarding GWI. The types of analyses to be performed will be wide ranging. Planned areas of focus may include:

  1. Characterization of the immune system and inflammatory signaling in collected samples at baseline and following maximal exercise exertion.
  2. Flow cytometry of blood and cerebrospinal fluid, RNA sequencing of PBMC subtypes, multiplex immunochemical analysis, NK cell functional analysis.
  3. Characterization of the pattern of microbiome in collected samples at baseline and following maximal exercise exertion.
  4. Shotgun metagenomics of bacterial genetic material
  5. Characterization of bioenergetics, autonomic, and metabolic function in collected samples at baseline and following maximal exercise exertion.
  6. Mitochondrial plasmid genotyping, pulmonary spirometry, gas exchange measurements during exercise, metabolic chamber measurements of total body energy use, metabolomic analysis of stool, mitochondrion proteomics and metabolomics from muscle, and functional respiration of PBMCs using extracellular flux mito stress assay.
  7. Characterization of physical and cognitive fatigue using functional magnetic resonance imaging and transcranial magnetic stimulation at baseline and following maximal exercise exertion.
  8. Characterization of neurocognition at baseline and following maximal exercise exertion.

Details
Condition Gulf War Illness
Clinical Study IdentifierNCT05375812
SponsorNational Institute of Neurological Disorders and Stroke (NINDS)
Last Modified on16 September 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Inclusion criteria for all participants
Ability to provide informed consent
Stated willingness to comply with all study procedures and availability for the duration of the study
Age 45-65 at time of enrollment
Veterans who were deployed to Gulf Region ODS/S between August 1990 - June 1991
Self-reported completion of at least the seventh grade of school
Fluency in speaking, reading, and understanding English
Underwent screening as part of the VA IN-DEPTH study and were unanimously determined to be eligible by the IN-DEPTH Adjudication Committee
Agree not to smoke in the 4 hours prior to CPET procedure
Additional inclusion criteria for veterans with GWI
A self-reported illness narrative of the development of chronic multi-symptom illness within three years of deployment to ODS/S. The chronic illness symptoms may have an acute onset or have become progressively worse within 3 years after deployment
Documentation of meeting GWI criteria as part of the VA IN-DEPTH study

Exclusion Criteria

Exclusion criteria for all veterans
Current or past psychotic disorder including depression with psychosis, bipolar disorder with psychotic symptoms and schizophrenia
Current DSM-5-defined major depression disorder, generalized anxiety disorder, posttraumatic stress disorder, panic disorder, or obsessive-compulsive disorder unless managed for more than six months with a stable treatment regimen
Current or past substance use disorder within last five years as diagnosed on the Structured Clinical Interview for DSM-5 (SCID-5). Prior or prescription marijuana use within the past five years will not be an exclusion
Current suicidal ideation
History of head injury leading to moderate or severe traumatic brain injury, as detailed by loss of consciousness for greater than 30 minutes, a Glasgow Coma Score of 12 or less at the time of injury, post-traumatic amnesia greater than one day, or brain-scan changes related to a head injury. Persons having a history of mild TBI (mTBI) will not be excluded
Women who are pregnant, breastfeeding, or are within one-year post-partum
Current or previous malignancy. A history of malignancy that has fully resolved with surgical resection only (e.g. no chemotherapy, radiation therapy, or immunotherapy) will be allowed
Current systemic immunologic disorders (e.g. Type 1 diabetes, rheumatoid arthritis). Local immunological disorder (e.g. atopic dermatitis, stable autoimmune thyroid disease) and allergic disorders will be allowed
Current or previous long-term immune suppressive therapy. Systemic steroid use, even short-term, must not have been used within the month prior to enrollment
Any medical condition that would make the study procedures risky for the participant (e.g. congestive heart failure, coronary artery disease, chronic obstructive pulmonary disease, severe osteoarthritis, exercise-induced angina and poorly controlled asthma)
Active participation in a clinical protocol (e.g. anti-inflammatory drug intervention study) which includes an intervention that may affect the results of the current study
Inability to perform the bicycling exercise task. (e.g. coronary artery disease, not having a lower limb, disabling stroke)
Not willing to allow for research data and samples to be shared broadly with other researchers
Symptom severity that makes it impossible for the volunteer to travel to NIH for extended inpatient evaluation
Use of medications with a high-risk for withdrawal-related complications (i.e. long-acting opiates or benzodiazepines)
Claustrophobia (metabolic chamber)
Exclusion criteria for participants undergoing TMS
Pacemaker, implanted pump, stimulator, cochlear implant or metal objects inside the eye or skull
A personal history of seizure disorder
Exclusion criteria for participants undergoing MRI
Metal in the body which would make having an MRI scan unsafe, such as pacemakers, stimulators, pumps, aneurysm clips, metallic prostheses, artificial heart valves, cochlear implants or shrapnel fragments, or having a history of being a welder or metal worker, since small metal fragments may be in the eye
Substantial claustrophobia
Inability to lie on back for up to 2 hours
Any condition that would make gadolinium administration a contraindication
Exclusion criteria for Healthy Veteran Soldiers
Meets modified Kansas criteria for GWI
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