Hyperbaric Oxygen Therapy Compared to Pharmaceutical in Fibromyalgia With Emotional Trauma

Hyperbaric Oxygen Therapy vs. Pharmaceutical Therapy in Patients Suffering From Fibromyalgia That Was Induced by Emotional Trauma: Prospective, Randomized, Two Active Arms Clinical Trial

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).

Study Overview

• Status: Completed
• Conditions: Fibromyalgia; Emotional Trauma
• Intervention / Treatment: Device: Hyperbaric oxygen therapy (HBOT) treatment; Drug: Cymbalta / Lyrica - Drug treatment

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.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Rishon LeZiyyon, Israel
    • hyperbaric center Asaf harofe medical center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 46 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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 (HBOT) treatment; 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
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 - Drug treatment; one of the two medications currently licensed for the treatment of FMS in Israel, i.e. Cymbalta and Lyrica. 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fibromyalgia Impact Questionnaire (FIQ) questionnaire	Fibromyalgia Impact Questionnaire (FIQ) questionnaire score at the end of treatment period (HBOT/pharmaceutical). Score range 0-100, higher score means worse outcome	at 3 months
Fibromyalgia Impact Questionnaire (FIQ) questionnaire	Fibromyalgia Impact Questionnaire (FIQ) questionnaire score at the end of follow up period (HBOT/pharmaceutical). Score range 0-100, higher score means worse outcome	at 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Widespread pain index questionnaire	Fibromyalgia syndrome symptoms questionnaire named:Wide Spread Pain Index (scale 0-19, higher score means worse outcome)	at baseline, 3 months, 6 months
Symptoms severity scale questionnaire	Fibromyalgia syndrome symptoms questionnaire named:Symptom Severity Scale (SSS) (scale 0-12, higher score means worse outcome)	at baseline, 3 months, 6 months
Post traumatic stress disorder (PTSD) symptoms scale (PSS) questionnaire	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	at baseline, 3 months, 6 months
Medical somatic dissociation questionnaire (MSDQ)	assess somatic dissociation in the healthcare system setting, Scale 5-130, higher score means worse outcome	at baseline, 3 months, 6 months
Recovery promoting relationships scale (RPRS)	assesses patient-therapist relationships from the patient's perspective.	at baseline, 3 months, 6 months
the brief symptom inventory (BSI-18)	evaluate psychological distress, three sub-scales: depression, anxiety, and somatization. scale of 0-24, higher score means worse outcome.	at baseline, 3 months, 6 months
Beck depression inventory (BDI)	a 21-question multiple choice self-report inventory, designed to measure severity of depression. scale of 0-63, higher score means worse outcome	at baseline, 3 months, 6 months
Short form health survey (sf-36)	Quality of life questionnaire, scale of 0-100, higher score means better outcome	at baseline, 3 months, 6 months
patient's global impression of change PGIC questionnaire	patient's global impression of change questionnaire, scale of 1-7, higher score means better outcome	at 3 months, at 6 months
draw a person (DAP) assignment	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	at baseline, 3 months, 6 months
Heat pain threshold	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.	at baseline, 3 months
conditioned pain modulation using Heat test-stimulus (HTS)	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	at baseline, 3 months
Cerebral blood volume	Cerebral blood volume (in milliliter) will be measured using perfusion MRI protocol Dynamic susceptibility contrast (DSC).	at baseline, 3 months
Cerebral blood Flow	Cerebral blood volume (in milliliter/min) will be measured using perfusion MRI protocol Dynamic susceptibility contrast (DSC).	at baseline, 3 months
Fractional anisotropy	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)	at baseline, 3 months
Mean diffusivity	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).	at baseline, 3 months
Brain function imaging	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).	at baseline, 3 months
Metabolic Brain function imaging	Brain Single photon emission computed tomography (SPECT) will be conducted.	at baseline, 3 months
Brain functionality	FMRI tasks will evaluate brain function during cognitive (working memory task) and emotional tasks (emotion recognition task)	at baseline, 3 months
NeuroTrax	computerized cognitive evaluation battery	at baseline, 3 months
CANTAB Cambridge Neuropsychological Test Automated Battery	computerized cognitive evaluation battery	at baseline, 3 months
Physical activity	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	at baseline, 3 months
Inflammatory cytokines	Blood Tests will include: IL-1, IL-6, Tumor necrosis factor-alpha, C-reactive protein (CRP).	at baseline, 3 months
Endocrine system	Free cortisol, Adrenocorticotropic hormone (ACTH) in blood tests and a hair sample for cortisol levels	at baseline, 3 months

Collaborators and Investigators

• Sponsor: Assaf-Harofeh Medical Center
• Collaborators: The Emili Sagol Creative Arts Therapies Research Center
• Investigators: Principal Investigator: Shai a Efrati, MD, Asaf-Harofhe MC

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2020
• Primary Completion (Actual): November 30, 2023
• Study Completion (Actual): November 30, 2023

Study Registration Dates

• First Submitted: March 3, 2020
• First Submitted That Met QC Criteria: March 18, 2020
• First Posted (Actual): March 20, 2020

Study Record Updates

• Last Update Posted (Actual): April 21, 2026
• Last Update Submitted That Met QC Criteria: April 16, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Diseases; Rheumatic Diseases; Fibromyalgia; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Respiratory Therapy; Thiophenes; Oxygen Inhalation Therapy; Duloxetine Hydrochloride; Therapeutics; Hyperbaric Oxygenation
• Other Study ID Numbers: 0008-20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No