START & STOPP in GWI
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Psychiatric |
| Therapuetic Areas: | Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 6/20/2018 |
| Start Date: | February 2016 |
| End Date: | September 30, 2020 |
Gulf War Illness (GWI) veterans were divided into 2 pathophysiological groups based on their
orthostatic tachycardia responses after submaximal exercise. Two thirds had normal increases
of 10 to 15 beats per minute between recumbent and standing both before and after exercise.
These were termed the Stress Test Originated Phantom Perception (STOPP) phenotype. In
contrast, one third had increases in heart rate of more than 30 beats per minute indicating
that exercise induced postural tachycardia; there were the Stress Test Activated Reversible
Tachycardia (START) group. This study aimed to confirm the original findings of Rayhan
(2013).
orthostatic tachycardia responses after submaximal exercise. Two thirds had normal increases
of 10 to 15 beats per minute between recumbent and standing both before and after exercise.
These were termed the Stress Test Originated Phantom Perception (STOPP) phenotype. In
contrast, one third had increases in heart rate of more than 30 beats per minute indicating
that exercise induced postural tachycardia; there were the Stress Test Activated Reversible
Tachycardia (START) group. This study aimed to confirm the original findings of Rayhan
(2013).
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.
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.
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.
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