Mechanisms of Mitochondrial Defects in Gulf War Syndrome

The purpose of the study is to investigate possible causes for Gulf War Syndrome. Gulf War Syndrome is associated with increased incidences of amyotrophic lateral sclerosis (Lou Gehrig's Disease), pain syndromes, muscle complaints that include fatigue and myalgias (muscle pain), as well as other neurological symptoms. Abnormalities in the part of the cell known as mitochondria have been delineated in Gulf War Syndrome. Mitochondria are the "power plants" of the body. Mitochondria take the food you eat and break the food down into a form of energy that the body can use. The investigators propose that Gulf War Syndrome is determined by a complex interaction of factors that interfere with mitochondrial function. This study will be the first investigation of mitochondrial function in Gulf War Syndrome. The investigators objective is to establish the cause for symptoms in affected veterans, develop testing that can more easily identify Gulf War Syndrome, and ultimately develop treatment protocols for Gulf War Syndrome.

Study Overview

• Status: Completed
• Conditions: Gulf War Syndrome; Mitochondrial Disease
• Intervention / Treatment: Procedure: Skin biopsy; Procedure: Blood Collection

• Study Type: Observational
• Enrollment (Actual): 26

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Medical Neurogenetics, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Gulf War Veterans who have been diagnosed with Gulf War Syndrome

Description

Inclusion Criteria:

• Short-term memory loss or a severe inability to concentrate that affects work, school or other normal activities
• Muscle Pain, myalgias
• Pain without redness or swelling in a number of joints
• Intense or changing patterns of headaches
• Unrefreshing sleep
• After any exertion, weariness that lasts for more than a day

Exclusion Criteria:

• Organ failure (e.g. emphysema, cirrhosis, cardiac failure, chronic renal failure)
• Chronic infections (e.g. HIV/AIDS, hepatitis B or C)
• Rheumatic and chronic inflammatory diseases (e.g. systemic lupus erythematosis, Sjogren's syndrome, rheumatoid arthritis, inflammatory bowel disease, chronic pancreatitis.)
• Major neurologic diseases (e.g. multiple sclerosis, neuromuscular diseases, epilepsy or other disease requiring ongoing medication that could cause fatigue, stroke, head injury with residual neurologic deficits)
• Diseases requiring systemic treatment (e.g. organ or bone marrow transplantation; systemic chemotherapy; radiation of brain, thorax, abdomen, or pelvis)
• Major endocrine diseases (e.g. hypopituitarism, adrenal insufficiency)
• Myocardial infarction, heart failure
• Morbid obesity (body mass index >40)
• Permanent psychiatric exclusions: Lifetime diagnoses of bipolar affective disorders, schizophrenia or any subtype, delusional disorders of any subtype, dementias of any subtype, organic brain disorders, and alcohol or substance abuse within 2 years before onset of the fatiguing illness.
• History of allergic reaction to lidocaine
• History of keloid formation with skin incisions.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Gulf War Syndrome patients; Gulf War veterans who have been diagnosed with Gulf War Syndrome.	Procedure: Skin biopsy; A small skin sample will be obtained from the patients arm which is approximately the size of the top of a thumbtack (a small circle no more than a 1/4 inch across); Other Names: skin sample; Procedure: Blood Collection; Approximately 45ml or 3 tablespoons for blood will be drawn from a vein in the patient's forearm.; Other Names: phlebotomy; blood draw

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterize mitochondrial cellular energetics in Gulf War Syndrome patients	After collecting a skin and blood sample, mitochondrial cellular energetics in Gulf War Syndrome patients will be characterized by: 1. high resolution respirometry of intact cells, 2. quantitative analysis of individual mitochondrial proteins, 3. analysis of intact OXPHOS enzyme complexes and supercomplexes, 4. in gel enzyme activity assessment of intact OXPHOS enzyme complexes and supercomplexes, 5. mitochondrial DNA (mtDNA) copy number quantitation to assess for defects in regulation mtDNA replication and 6. cellular coenzyme Q10 quantitation.	approximately 2 years; once all data has been collected from study participants

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mitochondrial DNA	Assess the mitochondrial DNA (mtDNA) from each patient with Gulf War Syndrome for mtDNA mutations by whole genome sequencing of leukocyte and skin cell mtDNA.	approximately 2 years; once all data has been collected from study participants.

Collaborators and Investigators

• Sponsor: Medical Neurogenetics, LLC
• Collaborators: United States Department of Defense
• Investigators: Principal Investigator: John M Shoffner, MD, Medical Neurogenetics

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: December 17, 2010
• First Submitted That Met QC Criteria: December 20, 2010
• First Posted (Estimate): December 21, 2010

Study Record Updates

• Last Update Posted (Estimate): April 13, 2015
• Last Update Submitted That Met QC Criteria: April 10, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Gulf War Syndrome; Gulf War Illness; Mitochondrial defects; Mitochondrial disorders; Persian Gulf Syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Disease; Occupational Diseases; Syndrome; Mitochondrial Diseases; Persian Gulf Syndrome
• Other Study ID Numbers: H09378; GW080138 (Other Grant/Funding Number: Department of Defense CDMRP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No