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Exertional Exhaustion in Chronic Fatigue Syndrome

Primary Purpose

Chronic Fatigue Syndrome

Status

Completed

Phase

Not Applicable

Locations

Study Type

Interventional

Intervention

Submaximal bicycle exercise stress test on Days 1 and 2

About this trial

This is an interventional basic science trial for Chronic Fatigue Syndrome

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

CFS and healthy subjects

Exclusion Criteria:

HIV / AIDS subjects
Pregnant women
Lactation
Cognitive impairment, mental retardation, severe head injury, stroke, proven multiple sclerosis, "melancholic" suicidal major depression, schizophrenia, Alzheimer's disease, "mild cognitive impairment" (MCI), other dementia, or other serious neurological diseases
Brain injury. stroke, severe head injury (concussion, severe motor vehicle accidents), bleeding into brain, have been unconscious for more than 1 day (in a coma), seizures, brain inflammation such as multiple sclerosis or lupus.
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, congestive heart failure, heart valve disease, 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, kidney disease on dialysis, liver disease (alcoholic cirrhosis, hepatitis B, hepatitis C), inflammatory bowel disease (Crohn's disease, ulcerative colitis), or cancer Subjects may participate if they have well-controlled diabetes or thyroid disease.

Any other chronic disease with chronic pain, fatigue and thinking problems (cognitive impairment) that would limit the ability to complete the questionnaires and other tests.

Amputation that would prevent bicycle exercise.
Medications. Drugs that interfere with heart, lung, brain and nerve function
Drinking and Smoking. You will have to stop caffeine (coffee, tea, soft drinks), alcohol, cannabis and nicotine products (smoking) for 3 days before the study, and the full period of the testing.
Difficulties Drawing Blood.
Children under the age of 18 years
Incarcerated people (in jail)
Alcohol or substance abuse in the past 6 months.
English: Subjects must be able to speak and understand English to be able to understand the tests and other instructions during the study.
Disruptive: Subjects who are disruptive or may reveal medical information about other subjects will be excluded.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Arm Label

Chronic Fatigue Syndrome

Sedentary Control

Arm Description

Inclusion and exclusion criteria based on 1994 Center for Disease Control ("Fukuda") criteria of persistent, disabling, moderate to severe fatigue that was relieved by rest, plus at least 4 of the 8 following ancillary features: cognitive dysfunction affecting short term memory or concentration, sore throat, sore lymph nodes, sore muscles, sore joints, headache, sleep disturbance, and exertional exhaustion (post-exertional malaise). Intervention: Procedure/Surgery: Submaximal bicycle exercise stress test on Days 1 and 2

Subjects who lived a sedentary lifestyle, did not meet Chronic Fatigue Syndrome criteria, and did not have any exclusionary chronic medical, psychiatric or other conditions were our Sedentary Control subjects. By design, this control group included controlled Type II diabetes and thyroid disease, chronic idiopathic fatigue, hypertension (other heart disease excluded) and other stable medical conditions. This variety of subjects were included to prevent ceiling (CFS) vs. floor (control) effects if the control group had totally pristine subjects with zero health issues. Intervention: Procedure/Surgery: Submaximal bicycle exercise stress test on Days 1 and 2

Outcomes

Primary Outcome Measures

Change in blood oxygenation level dependent (BOLD) patterns of brain blood flow during cognitive testing

MRI with cognitive tasks were performed before Day 1 exercise and compared to after the Day 2 exercise.

Secondary Outcome Measures

Postural change in heart rate and heart rate variability after exercise

Heart rates were recorded while subjects resting supine for 5 minutes, and during 5 minutes of standing. The change in heart rate (deltaHR) was calculated.

Pressure-induced pain (systemic hyperalgesia) by dolorimetry

A strain gauge (algometer, dolorimeter) was pressed over 18 traditional fibromyalgia tender point locations at a slow rate < kg/sec with the subject instructed to tell the operator to stop pushing as soon as they felt pain.

Full Information

NCT ID

NCT03567811

First Posted

April 20, 2018

Last Updated

June 18, 2019

Sponsor

Georgetown University

1. Study Identification

Unique Protocol Identification Number

NCT03567811

Brief Title

Exertional Exhaustion in Chronic Fatigue Syndrome

Official Title

Exertional Exhaustion in Chronic Fatigue Syndrome

Study Type

Interventional

2. Study Status

Record Verification Date

June 2019

Overall Recruitment Status

Completed

Study Start Date

August 1, 2013 (Actual)

Primary Completion Date

July 31, 2018 (Actual)

Study Completion Date

July 31, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Georgetown University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

Post-exertional malaise was modeled by having Chronic Fatigue Syndrome (CFS) and sedentary control subjects perform submaximal exercise on 2 consecutive days with objective changes in brain function measured by magnetic resonance imaging (MRI) during cognitive tests before and after the 2 exercise sessions.

Detailed Description

Chronic Fatigue Syndrome (CFS) and sedentary control subjects answered on-line advertisements and word-of-mouth communications. Candidates gave verbal informed consent to discuss their medical history during a telephone interview. If the met inclusion and exclusion criteria, they were assigned an log-in code and password to complete an extensive on-line questionnaire, and were scheduled for the 3 day in-patient study. On the Screening Day subjects completed written informed consent, history and physical, screening blood work, mental status exam, heart rate variability for orthostasis, and dolorimetry for systemic hyperalgesia. On Exercise Day 1, subjects had magnetic resonance imaging (MRI) for structure (MPRAGE), white matter integrity (diffusion tensor imaging, DTI), and blood oxygenation level dependent (BOLD) analysis during working memory tasks. The tasks were the simple stimulus-response 0-back "see a letter, push a button" task, and the difficult continuous 2-back task "see a string of letters, remember the letters in order, press the button for the letter seen 2 previously ("2-back)". The submaximal exercise test was performed in identical fashion on day 1 and day 2. Subjects rested on a bicycle ergometer for 5 minutes for baseline cardiopulmonary (VO2) measurements. They began pedalling with resistance increased in step wise fashion until their heart rate reached 70% of predicted maximum heart rate (pHR = 220 - age). They pedaled 25 minutes at 70% or until they felt they had their personal maximum effort (e.g. Borg Exertional Scale 19/20). If they reached 25 minutes, then resistance was increased until they reached 85% of pHR. Continuous EKG, symptoms and VO2 were followed from rest until 5 minutes after peak exercise. Heart rate variability and symptoms were assessed during recumbent and standing posture to assess orthostatic intolerance. On Exercise Day 2, the same methods were used, but the order was reversed with the submaximal exercise test first, followed by the identical MRI protocol.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Fatigue Syndrome

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Model Description

All subjects were participated in an identical protocol. Outcomes were compared between control and Chronic Fatigue Syndrome subjects.

Masking

None (Open Label)

Masking Description

All control and Chronic Fatigue Syndrome subjects were treated in identical fashion.

Allocation

Non-Randomized

Enrollment

72 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Chronic Fatigue Syndrome

Arm Type

Other

Arm Description

Arm Title

Sedentary Control

Arm Type

Other

Arm Description

Intervention Type

Procedure

Intervention Name(s)

Submaximal bicycle exercise stress test on Days 1 and 2

Intervention Description

Identical submaximal stress tests were performed on both days to see if Day 1 exercise reduced performance on Day 2, or caused changes between BOLD scans during cognitive testing between Day 1 and Day 2.

Primary Outcome Measure Information:

Title

Change in blood oxygenation level dependent (BOLD) patterns of brain blood flow during cognitive testing

Description

MRI with cognitive tasks were performed before Day 1 exercise and compared to after the Day 2 exercise.

Time Frame

Day 1 (pre-exercise) and Day 2 (after 2nd exercise)

Secondary Outcome Measure Information:

Title

Postural change in heart rate and heart rate variability after exercise

Description

Heart rates were recorded while subjects resting supine for 5 minutes, and during 5 minutes of standing. The change in heart rate (deltaHR) was calculated.

Time Frame

Before exercise. 1, 3, 8, 24 and 36 hours after exercise

Title

Pressure-induced pain (systemic hyperalgesia) by dolorimetry

Description

Time Frame

10 am each day for 4 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: CFS and healthy subjects Exclusion Criteria: HIV / AIDS subjects Pregnant women Lactation Cognitive impairment, mental retardation, severe head injury, stroke, proven multiple sclerosis, "melancholic" suicidal major depression, schizophrenia, Alzheimer's disease, "mild cognitive impairment" (MCI), other dementia, or other serious neurological diseases Brain injury. stroke, severe head injury (concussion, severe motor vehicle accidents), bleeding into brain, have been unconscious for more than 1 day (in a coma), seizures, brain inflammation such as multiple sclerosis or lupus. 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, congestive heart failure, heart valve disease, 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, kidney disease on dialysis, liver disease (alcoholic cirrhosis, hepatitis B, hepatitis C), inflammatory bowel disease (Crohn's disease, ulcerative colitis), or cancer Subjects may participate if they have well-controlled diabetes or thyroid disease. Any other chronic disease with chronic pain, fatigue and thinking problems (cognitive impairment) that would limit the ability to complete the questionnaires and other tests. Amputation that would prevent bicycle exercise. Medications. Drugs that interfere with heart, lung, brain and nerve function Drinking and Smoking. You will have to stop caffeine (coffee, tea, soft drinks), alcohol, cannabis and nicotine products (smoking) for 3 days before the study, and the full period of the testing. Difficulties Drawing Blood. Children under the age of 18 years Incarcerated people (in jail) Alcohol or substance abuse in the past 6 months. English: Subjects must be able to speak and understand English to be able to understand the tests and other instructions during the study. Disruptive: Subjects who are disruptive or may reveal medical information about other subjects will be excluded.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kristen Katopol

Organizational Affiliation

IRB Director

Official's Role

Study Chair

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

RedCap

IPD Sharing Time Frame

2019

IPD Sharing Access Criteria

open

Citations:

PubMed Identifier

31159884

Citation

Garner R, Baraniuk JN. Orthostatic intolerance in chronic fatigue syndrome. J Transl Med. 2019 Jun 3;17(1):185. doi: 10.1186/s12967-019-1935-y.

Results Reference

result

PubMed Identifier

30666170

Citation

Timbol CR, Baraniuk JN. Chronic fatigue syndrome in the emergency department. Open Access Emerg Med. 2019 Jan 11;11:15-28. doi: 10.2147/OAEM.S176843. eCollection 2019.

Results Reference

result

PubMed Identifier

23898301

Citation

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.

Results Reference

result

PubMed Identifier

30854252

Citation

Baraniuk JN. Chronic Fatigue Syndrome prevalence is grossly overestimated using Oxford criteria compared to Centers for Disease Control (Fukuda) criteria in a U.S. population study. Fatigue. 2017;5(4):215-230. doi: 10.1080/21641846.2017.1353578. Epub 2017 Jul 21.

Results Reference

result

PubMed Identifier

29127316

Citation

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.

Results Reference

result

PubMed Identifier

29674668

Citation

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.

Results Reference

result

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Exertional Exhaustion in Chronic Fatigue Syndrome

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