- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03560830
START & STOPP in GWI (START)
START & STOPP in GWI Stress Test Activated Reversible Tachycardia & Stress Test Originated Phantom Perception in Gulf War Illness
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Gulf War Illness (GWI) veterans had heart rate and blood pressure measured lying down, and then for 5 minutes standing up. Before exercise, all GWI had normal changes of 10 to 15 beats per minute upon standing up. Then they had submaximal bicycle exercise stress tests. Rayhan et al. (2013) discovered that two thirds of the subjects had the same, unchanged response of about 10 to 15 beats per minute upon standing both before and after exercise. These were termed the Stress Test Original Phantom Perception (STOPP) phenotype. In contrast, one third of GWI veterans were found to have normal postural changes before exercise, but all the stress tests they had larger changes in heart rate of over 30 beats per minute. They were termed the Stress Test Activated Reversible Tachycardia (START) phenotype.
The importance of the START phenotype was indicated by finding that they had brain stem atrophy by MRI voxel based morphometry, reduced brain blood flow and activation during a cognitive task performed in the fMRI scanner, and differences in biomarkers compared to STOPP and sedentary control subjects.
This study was designed to use the identical exercise protocol to verify or refute the presence of START and STOPP phenotypes in GWI.
The incremental change in heart rate between recumbent and standing (Delta HR) was determined by having subjects lie quietly at rest. Heart rate and blood pressure was measured at 1 minute intervals. The average recumbent heart rate was determined. Then subjects stood up without assistance. Beginning 1 minute after standing up, heart rate was measured at 1 minute intervals for 5 minutes. Delta HR was found by subtracting each of the 5 standing measurements minus the average recumbent heart rate. If a subject had 2 or more Delta HR measurements of 30 beats per minute or greater while standing, they were called Stress Test Activated Reversible Tachycardia (START).
The threshold of 30 beats per minute for Delta HR was based on the criteria for Postural Orthostatic Tachycardia Syndrome (POTS). However, START subjects had normal Delta HR of 10 to 15 before exercise, and so did not have POTS. This was a key finding of the original study that we plan to verify in this study.
Study Design:
Pre-exercise recumbent and standing heart rate measurements and m Magnetic resonance imaging (MRI).
Exercise: Submaximal bicycle exercise stress test. Subjects were monitored while sitting on the bike for 5 minutes. Cycling started with a gradual increase in resistance to increase heart rate to 70% of maximum predicted heart rate (pHR = 220-Age). Cycling continued at 70%pHR for 25 minutes or until the subject wanted to stop. After 25 minutes, the exercise level was increased gradually to reach 85%pHR equivalent to a cardiac stress test. After stopping, heart rate was measured for 5 more minutes while sitting.
Post-Exercise: Recumbent and standing heart rate measurements were performed approximately 3, 8, 24 and 36 hours after exercise. Specific times could not be scheduled because of the timing of MRI scans and other procedures.
Outcome measure: DeltaHR was the difference between standing heart rates minus average recumbent heart rate. Changes in DeltaHR were measured for up to 48 hr after exercise.
START definition: DeltaHR of 30 more greater at 2 or more time points in the 48 hr after submaximal exercise.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
-
-
District of Columbia
-
Washington, District of Columbia, United States, 20007-2197
- Georgetown University
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
Gulf War Illness subjects: "Kansas" criteria of Lea Steele (2000). Healthy Veterans: Have never met criteria for GWI, Chronic Multisymptom Illness (CMI), or any of the other related conditions.
All subjects: A score of 24 or more on the Mini Mental Status Examination.
Exclusion Criteria:
HIV / AIDS subjects Pregnant women. Active duty military personnel. Children under age of 18 years Incarcerated people (in jail) Cognitive impairment such as mental retardation, severe head injury, stroke, proven multiple sclerosis, "melancholic" suicidal major depression, schizophrenia, dementia, Alzheimer disease, Parkinson's disease, brain injury, severe head injury, bleeding into brain, have been unconscious for more than 1 day (in a coma), seizures, multiple sclerosis, or other serious neurological disease.
Metal implants such as prostheses, wires, plates, or screws that may heat up in the magnetic resonance imaging scanner and cause harm.
Claustrophobia. Abnormal laboratory and questionnaire results. Heart, lung, kidney, arthritis, autoimmune, cancer, and other chronic illnesses, leg amputations, heart attacks (myocardial infarction), coronary artery disease, abnormal heart rhythms, uncontrolled high blood pressure or strokes, lung disease from smoking or other causes, painful, swollen or deformed joints related to arthritis or autoimmune diseases, weakness from nerve damage, liver disease (alcoholic cirrhosis), inflammatory bowel disease (Crohn's disease, ulcerative colitis), or cancer Medications. Drugs that interfere with heart, lung, brain and nerve function Problems Drawing Blood.
Subjects may participate if they have well controlled diabetes or thyroid disease.
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Control
Sedentary control subjects with no medical or psychiatric disorder
|
|
POTS GWI
GWI with Postural Orthostatic Tachycardia Syndrome (POTS) GWI veterans who had postural orthostatic tachycardia before exercise and after 2 submaximal exercise stress tests.
Postural orthostatic tachycardia was defined by 2015 Consensus as an increase in heart rate of greater than or equal to 30 beats per minute between recumbent (after 5 minutes of rest) and standing up.
Standing heart rates were measured every minute for 5 minutes.
Postural orthostatic tachycardia was defined if the change in heart rate was more than 30 beats per minute at at least 2 of the 5 standing time points.
The average change in heart rate did not have to be above 30.
There were 11 GWI POTS subjects.
|
|
START
START = Stress Test Activated Reversible Tachycardia One third of GWI veterans were found to have normal changes in heart rate between recumbent and standing (usual change ~10 to 15 beats per minute) BEFORE EXERCISE, but AFTER EXERCISE (submaximal exercise stress tests) they developed postural orthostatic tachycardia with changes in heart rate of 30 or more between recumbent and standing. The effect was transient as it lasted about 36 to 48 hr. The START group had brainstem atrophy and reduced brain activation during a cognitive task compared to sedentary control and other GWI subjects. |
|
STOPP
STOPP = Stress Test Originated Phantom Perception Two thirds of GWI veterans were found to have normal changes in heart rate between recumbent and standing (usual change ~10 to 15 beats per minute) both before and after 2 submaximal exercise stress tests. STOPP did not develop postural orthostatic tachycardia. their changes were equivalent to the sedentary control group. The STOPP group increased brain activation of the basal ganglia and anterior insula during a cognitive task compared to sedentary control subjects. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
START Phenotype
Time Frame: 48 hour
|
Delta heart rate (deltaHR) greater than 30 beats per minute within 48 hr of performing submaximal exercise stress test
|
48 hour
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: James N Baraniuk, Georgetown University
Publications and helpful links
General Publications
- Baraniuk JN, Shivapurkar N. Exercise - induced changes in cerebrospinal fluid miRNAs in Gulf War Illness, Chronic Fatigue Syndrome and sedentary control subjects. Sci Rep. 2017 Nov 10;7(1):15338. doi: 10.1038/s41598-017-15383-9. Erratum In: Sci Rep. 2018 Apr 19;8(1):6455.
- Rayhan RU, Washington SD, Garner R, Zajur K, Martinez Addiego F, VanMeter JW, Baraniuk JN. Exercise challenge alters Default Mode Network dynamics in Gulf War Illness. BMC Neurosci. 2019 Feb 21;20(1):7. doi: 10.1186/s12868-019-0488-6.
- Garner RS, Rayhan RU, Baraniuk JN. Verification of exercise-induced transient postural tachycardia phenotype in Gulf War Illness. Am J Transl Res. 2018 Oct 15;10(10):3254-3264. eCollection 2018.
- Baraniuk JN, Shivapurkar N. Author Correction: Exercise - induced changes in cerebrospinal fluid miRNAs in Gulf War Illness, Chronic Fatigue Syndrome and sedentary control subjects. Sci Rep. 2018 Apr 19;8(1):6455. doi: 10.1038/s41598-018-23238-0.
- Rayhan RU, Ravindran MK, Baraniuk JN. Migraine in gulf war illness and chronic fatigue syndrome: prevalence, potential mechanisms, and evaluation. Front Physiol. 2013 Jul 24;4:181. doi: 10.3389/fphys.2013.00181. eCollection 2013.
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2015-0579
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
- ANALYTIC_CODE
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Gulf War Syndrome
-
American UniversityBoston University; Massachusetts General Hospital; Georgetown University; Nova...RecruitingGulf War Syndrome | Gulf War IllnessUnited States
-
Roskamp Institute Inc.Boston University; United States Department of Defense; Palo Alto Veterans Institute...Recruiting
-
University of UtahVA Salt Lake City Health Care SystemWithdrawn
-
Baylor College of MedicineTexas A&M University; Michael E. DeBakey VA Medical CenterNot yet recruiting
-
Nova Southeastern UniversityBoston University; Weill Medical College of Cornell University; RTI InternationalRecruiting
-
Georgetown UniversityU.S. Army Medical Research and Development CommandCompletedGulf War Illness | Persian Gulf War SyndromeUnited States
-
South Florida Veterans Affairs Foundation for Research...Unknown
-
VA Office of Research and DevelopmentCompleted
-
University of Alabama at BirminghamCongressionally Directed Medical Research ProgramsRecruiting
-
Baylor College of MedicineMichael E. DeBakey VA Medical CenterTerminated
Clinical Trials on 2 submaximal exercise stress tests
-
Georgetown UniversityU.S. Army Medical Research and Development CommandCompleted
-
Georgetown UniversityCompletedChronic Fatigue Syndrome
-
University of Nevada, Las VegasRecruitingDown SyndromeUnited States
-
Marquette UniversityRecruitingHealthy SubjectsUnited States
-
Towson UniversityCompletedEndothelial Dysfunction | Arterial StiffnessUnited States
-
VA Office of Research and DevelopmentCompleted
-
Technical University of MadridRecruiting
-
Foundation University IslamabadRecruiting
-
Dokuz Eylul UniversityCompleted
-
Duke UniversityNational Institute on Aging (NIA); Bryan Alzheimer's Disease Research Center; Duke University Center for the Study of Aging and Human DevelopmentCompleted