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Hyperbaric Oxygen Therapy Compared to Pharmaceutical in Fibromyalgia With Emotional Trauma

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ClinicalTrials.gov Identifier: NCT04316702
Recruitment Status : Recruiting
First Posted : March 20, 2020
Last Update Posted : March 20, 2020
Sponsor:
Collaborator:
The Emili Sagol Creative Arts Therapies Research Center
Information provided by (Responsible Party):
Prof. Shay Efrati, Assaf-Harofeh Medical Center

Brief Summary:

The investigators have previously studied the efficacy of hyperbaric oxygen therapy (HBOT) as a treatment for Fibromyalgia syndrome (FMS) in a prospective, active control, crossover clinical trial. The results demonstrated significant amelioration of all FMS symptoms, with significant improvement in life quality; furthermore, the investigators were able to demonstrate significant neuroplasticity on SPECT imaging, with a decrease of the hyperactivity in posterior regions and elevation of the reduced activity in frontal areas.

In this study, the investigators intend to both repeat and expand the investigator's previous findings, treating FMS patients with history of emotional trauma with HBOT, while performing an extensive of evaluation both before and after treatment.

In the current study, the investigators plan to compare HBOT to current standard of care of FMS (pharmacological and non - pharmacological).


Condition or disease Intervention/treatment Phase
Fibromyalgia Emotional Trauma Device: Hyperbaric oxygen therapy Drug: Cymbalta / lyrica Not Applicable

Detailed Description:

The study will include 60 fibromyalgia patients in whom emotional trauma, such as childhood abuse, could be considered as the trigger for FMS. Each participant will be examined at the time of recruitment and a diagnosis of FMS will be verified, based on the updated 2016 diagnostic criteria. In the current study the investigators will recruit patients not currently being treated with the target medications (Lyrica or Cymbalta).

Patients will undergo randomization upon recruitment to one of the two study groups. One group will proceed to a course of HBOT treatment while the second group will commence with standard treatment for FMS, as outlined in the Israeli guidelines for the diagnosis and treatment of FMS .

HBOT protocol: a total of 60 daily hyperbaric oxygen treatment sessions will be administrated 5 days per week. 60 sessions will include exposure of 90 minutes to 100% at 2 Absolute atmospheres (ATA), with 5 minutes air breaks every 20 minutes.

Pharmaceutical protocol: patients will be offered pharmacological treatment with one of the two medications currently licensed for the treatment of FMS in Israel, i.e. Cymbalta and Lyrica. Treatment with Lyrica will start at a dose of 75 mg twice a day, at morning and at bedtime, while treatment with Cymbalta will start at a dose of 30 mg a day (in the morning). After a period of 2 weeks, patients will be evaluated and dose will be adjusted as necessary and tolerated, up to the maximum dosage recommended for FM. Patients may also be switched from one medication to the other according to clinical judgment of the physician.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: randomized controlled trial using conventional pharmacotherapy treatment compared to hyperbaric oxygen therapy
Masking: Double (Investigator, Outcomes Assessor)
Masking Description: randomization by computer, the patient and her primary care physician will know the treatment received. Any side effects during therapy will be reported to the care providers and nurses and physicians unrelated to the study. Investigators and outcome assessors will not know the patient's arm.
Primary Purpose: Treatment
Official Title: Hyperbaric Oxygen Therapy vs. Pharmaceutical Therapy in Patients Suffering From Fibromyalgia That Was Induced by Emotional Trauma: Prospective, Randomized, Two Active Arms Clinical Trial
Estimated Study Start Date : March 2020
Estimated Primary Completion Date : March 2023
Estimated Study Completion Date : March 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Hyperbaric Oxygen
60 daily hyperbaric oxygen treatment sessions will be administrated 5 days per week. Each session will include exposure of 90 minutes to 100% at 2 ATA, with 5 minutes air breaks every 20 minutes
Device: Hyperbaric oxygen therapy
60 HBOT sessions at 2 ATA 100% oxygen

Active Comparator: Pharmacotherapy
Two medications currently licensed for the treatment of FM in Israel, i.e. Cymbalta and Lyrica. Treatment with Lyrica will start at a dose of 75 mg twice a day, at morning and at bedtime, while treatment with Cymbalta will start at a dose of 30 mg a day (in the morning). After a period of 2 weeks, patients will be evaluated and dose will be adjusted as necessary and tolerated, up to the maximum dosage recommended for FM. Patients may also be switched from one medication to the other according to clinical judgment of the physician.
Drug: Cymbalta / lyrica
one of the two medications currently licensed for the treatment of FMS in Israel, i.e. Cymbalta and Lyrica.




Primary Outcome Measures :
  1. Fibromyalgia Impact Questionnaire (FIQ) questionnaire [ Time Frame: at 3 months ]
    Fibromyalgia Impact Questionnaire (FIQ) questionnaire score at the end of treatment period (HBOT/pharmaceutical). Score range 0-100, higher score means worse outcome

  2. Fibromyalgia Impact Questionnaire (FIQ) questionnaire [ Time Frame: at 6 months ]
    Fibromyalgia Impact Questionnaire (FIQ) questionnaire score at the end of follow up period (HBOT/pharmaceutical). Score range 0-100, higher score means worse outcome


Secondary Outcome Measures :
  1. Widespread pain index questionnaire [ Time Frame: at baseline, 3 months, 6 months ]
    Fibromyalgia syndrome symptoms questionnaire named:Wide Spread Pain Index (scale 0-19, higher score means worse outcome)

  2. Symptoms severity scale questionnaire [ Time Frame: at baseline, 3 months, 6 months ]
    Fibromyalgia syndrome symptoms questionnaire named:Symptom Severity Scale (SSS) (scale 0-12, higher score means worse outcome)

  3. Post traumatic stress disorder (PTSD) symptoms scale (PSS) questionnaire [ Time Frame: at baseline, 3 months, 6 months ]
    a 17-item semi-structured interview that assesses the presence and severity of Diagnostic and Statistical Manual (DSM-IV) PTSD symptoms related to a single identified traumatic event in individuals with a known trauma history. scale 0-51, higher score means worse outcome

  4. Medical somatic dissociation questionnaire (MSDQ) [ Time Frame: at baseline, 3 months, 6 months ]
    assess somatic dissociation in the healthcare system setting, Scale 5-130, higher score means worse outcome

  5. Emotion regulation questionnaire (ERQ) [ Time Frame: at baseline, 3 months, 6 months ]
    assessing the emotional regulation strategies of Cognitive Reappraisal (scale 6-42) and Expressive Suppression (scale 4-24). higher score worse outcome.

  6. the brief symptom inventory (BSI-18) [ Time Frame: at baseline, 3 months, 6 months ]
    evaluate psychological distress, three sub-scales: depression, anxiety, and somatization. scale of 0-24, higher score means worse outcome.

  7. Beck depression inventory (BDI) [ Time Frame: at baseline, 3 months, 6 months ]
    a 21-question multiple choice self-report inventory, designed to measure severity of depression. scale of 0-63, higher score means worse outcome

  8. Short form health survey (sf-36) [ Time Frame: at baseline, 3 months, 6 months ]
    Quality of life questionnaire, scale of 0-100, higher score means better outcome

  9. patient's global impression of change PGIC questionnaire [ Time Frame: at 3 months, at 6 months ]
    patient's global impression of change questionnaire, scale of 1-7, higher score means better outcome

  10. draw a person (DAP) assignment [ Time Frame: at baseline, 3 months, 6 months ]
    self drawing tool, allows the expression of hidden or repressed thoughts and feelings in a relatively rapid and simple way by passing the censorship defensive mechanism

  11. Heat pain threshold [ Time Frame: at baseline, 3 months ]
    Heat pain threshold is determined as the minimum temperature causing pain. Thermal pain is induced with thermal electrode (thermode). Thermode temperature will initially be set at 32.0°C and gradually increase at a rate of 0.3°C/sec. Participants will be instructed to report when the sensation produced by the thermode changed from heat sensation to pain (heat-pain threshold). This procedure will be conducted three times for every subject and the mean of the trials will be calculated.

  12. conditioned pain modulation using Heat test-stimulus (HTS) [ Time Frame: at baseline, 3 months ]
    Following heat pain thresholds assessments, the thermode will be applied on the forearm for 120 seconds at constant temperature. The temperature will be individually adapted to induce a mean pain intensity of 50/100, Participant's pain intensity will be evaluated by numeric pain rating scale (NPRS) ranging from 0 (no pain) to 100 (most intense pain tolerable). The 120-second HTS will be done before and during cold water immersion of the contralateral hand in 10 Celsius degrees, using the same thermode temperature to measure conditioned pain modulation (CPM). CPM efficiency will be evaluated by computing the difference in mean pain intensity induced by the pressure stimulus and the Heat test-stimulus (HTS) before and during the Cold water immersion of the opposite hand. Thus, effective pain inhibitory mechanisms are represented by higher (positive) values

  13. Cerebral blood volume [ Time Frame: at baseline, 3 months ]
    Cerebral blood volume (in milliliter) will be measured using perfusion MRI protocol Dynamic susceptibility contrast (DSC).

  14. Cerebral blood Flow [ Time Frame: at baseline, 3 months ]
    Cerebral blood volume (in milliliter/min) will be measured using perfusion MRI protocol Dynamic susceptibility contrast (DSC).

  15. Fractional anisotropy [ Time Frame: at baseline, 3 months ]
    Brain microstructure imaging will evaluate fractional anisotropy (FA , scale 0-1 in each region of interest. The MRI protocol will include diffusion tensor imaging (DTI)

  16. Mean diffusivity [ Time Frame: at baseline, 3 months ]
    Brain microstructure imaging will evaluate mean diffusivity (MD, scale 0-1 in each region of interest. The MRI protocol will include diffusion tensor imaging (DTI).

  17. Brain function imaging [ Time Frame: at baseline, 3 months ]
    Resting state fMRI(rsfMRI or R-fMRI)- a method of functional brain imaging that can be used to evaluate regional interactions that occur when a subject is not performing an explicit task. This resting brain activity is observed through changes in blood flow in the brain which creates what is referred to as a blood-oxygen-level dependent (BOLD) signal that can be measured using functional Magnetic Resonance Imaging (fMRI).

  18. Metabolic Brain function imaging [ Time Frame: at baseline, 3 months ]
    Brain Single photon emission computed tomography (SPECT) will be conducted.

  19. Brain functionality [ Time Frame: at baseline, 3 months ]
    FMRI tasks will evaluate brain function during cognitive (working memory task) and emotional tasks (emotion recognition task)

  20. NeuroTrax [ Time Frame: at baseline, 3 months ]
    computerized cognitive evaluation battery

  21. CANTAB Cambridge Neuropsychological Test Automated Battery [ Time Frame: at baseline, 3 months ]
    computerized cognitive evaluation battery

  22. NIH toolbox [ Time Frame: at baseline, 3 months ]
    computerized cognitive evaluation battery

  23. Exercise - Maximal oxygen consumption [ Time Frame: at baseline, 3 months ]
    Participants will perform a standard test on a bicycle ergometer using a protocol based on increasing power per minute until exhaustion. Gas exchange will be analysed using the QuarK CPET (Cosmed Italy) device by a trained physiologist.

  24. Exercise - Anaerobic threshold oxygen consumption [ Time Frame: at baseline, 3 months ]
    Same CPET maximal test will be used for evaluation of the anaerobic threshold oxygen consumption by a trained physiologist.

  25. Physical activity [ Time Frame: at baseline, 3 months ]
    The daily physical activity will be objectively tracked by Garmin watch technology. The watch will be also wired during night for measurements of the time asleep, restless and awake, trackers help you understand each night to make the most of each day

  26. Inflammatory cytokines [ Time Frame: at baseline, 3 months ]
    Blood Tests will include: IL-1, IL-6, Tumor necrosis factor-alpha, C-reactive protein (CRP).

  27. Endocrine system [ Time Frame: at baseline, 3 months ]
    Free cortisol, Adrenocorticotropic hormone (ACTH) in blood tests and a hair sample for cortisol levels

  28. Epigenetics [ Time Frame: at baseline, 3 months ]
    Blood test for Epigenetic changes including telomere length, DNA methylation and RNA expression.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • FM diagnosis based on the widespread pain index (WPI) and the Symptom Severity Score (SSS).
  • Score at the trauma questionnaire indicating low, moderate or severe trauma in one of the criteria specified in the questionnaire.
  • Ability to provide informed consent
  • Age>18

Exclusion Criteria:

  • Presence of systemic inflammatory disorders including inflammatory rheumatological and autoimmune disorders.
  • History of traumatic brain injury (TBI)
  • Other FM etiologies
  • Currently or previously treated with Duloxetine (Cymbalta) or Pregabalin (Lyrica)
  • Contraindications to both Lyrica and Cymbalta
  • Major psychiatric disorder (such as major depression, schizophrenia, bi-polar disorder)
  • Previous suicidal attempt/s
  • Does not take part in psychotherapy on a weekly basis (minimum)
  • Previous HBOT for any other reason prior to their inclusion
  • Chest pathology (including active asthma)
  • Inner ear disease
  • Claustrophobia
  • Inability to perform awake brain MRI test
  • Chronic renal failure (eGFR< 60 ml/min)
  • Previous neurological conditions (eg. Epilepsy, neuromuscular diseases, metabolic diseases, etc.); Brain tumors; Skull base fractures; Active malignancy; s/p neurosurgery
  • Active Smoking
  • Pregnancy or not committing to not getting pregnant during the study period

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04316702


Contacts
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Contact: Rahav Boussi-Gross 089772492 rahav.b@gmail.com

Locations
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Israel
hyperbaric center Asaf harofe medical center Recruiting
Rishon lezion, Israel
Contact: shai efrati, Prof    089779393    efratishai@013.com   
Sponsors and Collaborators
Assaf-Harofeh Medical Center
The Emili Sagol Creative Arts Therapies Research Center
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Responsible Party: Prof. Shay Efrati, Head of Sagol center for hyperbaric medicine and research, Assaf-Harofeh Medical Center
ClinicalTrials.gov Identifier: NCT04316702    
Other Study ID Numbers: ASF-20-0008
First Posted: March 20, 2020    Key Record Dates
Last Update Posted: March 20, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Fibromyalgia
Myofascial Pain Syndromes
Wounds and Injuries
Muscular Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Neuromuscular Diseases
Nervous System Diseases
Duloxetine Hydrochloride
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Psychotropic Drugs
Serotonin and Noradrenaline Reuptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Antidepressive Agents
Dopamine Agents