Clinical trial NCT03325959: Hyperbaric Oxygen Compared to Pharmaceutical Therapies for Fibromyalgia Syndrome
Official title: Hyperbaric Oxygen vs. Standard Pharmaceutical Therapies for Fibromyalgia Syndrome - Prospective, Randomized Crossover Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Fibromyalgia
Hyperbaric Oxygen
Keywords: hyperbaric oxygen
HBOT
fibromyalgia
pain
Lead sponsor: Assaf-Harofeh Medical Center
Sponsor class: OTHER_GOV
First posted: 2017-10-30
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: randomized controlled trial using conventional pharmacotherapy treatment compared to hyperbaric oxygen therapy
Primary purpose: TREATMENT

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 the proposed study, the investigators intend to both repeat and expand our previous findings, treating FMS patients 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).

Detailed description: The study will include 70 fibromyalgia patients in whom physical trauma, such mild traumatic brain injury (mTBI), 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 medications specific for FMS, including anti-depression drugs, gabapentanoids and tricyclics, opiods and medical cannabis. Patients who are on such treatment will be required to discontinue treatment 2 weeks before recruitment.

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 \[41\]. These patients will be given detailed education regarding the nature of FMS as well as recommendations regarding non - pharmacological interventions recommended for FMS, including graded physical exercise, hydrotherapy, movement-meditative treatments (e.g. Tai Chi) and cognitive behavioral treatment (CBT).

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 at bedtime while treatment with Cymbalta will start at a dose of 30 mg a day (in the morning). After a period of 6 weeks patients will be evaluated and dose will be adjusted as necessary. Patients may also be switched from one medication to the other based according to clinical judgment.

Crossover: After 3 months of either pharmaceuitical or HBOT, once the 2nd evaluation is completed, all patients in both groups will be offered to switch to the alternative treatment group.

Eligibility criteria: Inclusion Criteria:

* FMS diagnosis, based on the updated 2016 diagnostic criteria
* previous physical trauma (such as traumatic brain injury)

Exclusion Criteria:

* the presence of systemic inflammatory disorders including inflammatory rheumatological and autoimmune disorders.
* active malignancy,
* chronic ongoing infection
* major psychiatric disorders (excluding anxiety)
* Patients currently or previously treated with Duloxetine (Cymbalta) or Pregabalin (Lyrica) will also be excluded
* previous HBOT for any other reason prior to their inclusion;
* Chest pathology incompatible with pressure changes (including active asthma);
* Inner ear disease
* Claustrophobia;
* Inability to perform awake brain MRI test;
* Previous neurologic conditions (eg. Epilepsy, neuromuscular diseases, metabolic diseases, etc.);
* Brain tumors;
* Skull base fractures;
* s/p neurosurgery that included: ventricular drainage, subdural hematomas drainage, epidural hematomas drainage, intracerebral hemorrhage evacuation. Depressed fracture surgery, (Patients suffering from Encephalomalacia per MRI imaging will not be excluded).
* Inability to provide informed consent

Primary outcomes:
measure: Visual analogue Scale (VAS)
timeFrame: at 3 months
measure: Visual analogue Scale (VAS)
timeFrame: at 6 months
Secondary outcomes:
measure: Global Pain Scale (GPS)
timeFrame: baseline, at 3 months, at 6 months
measure: Patient global impression of change
timeFrame: baseline, at 3 months, at 6 months
measure: Fibromyalgia Impact Questionnaire
timeFrame: baseline, at 3 months, at 6 months
measure: Wide Spread Pain Index
timeFrame: baseline, at 3 months, at 6 months
measure: Symptom Severity Scale
timeFrame: baseline, at 3 months, at 6 months
measure: SF-36 questionnaire
timeFrame: baseline, at 3 months, at 6 months
measure: Medical Outcome Sleep Scale
timeFrame: baseline, at 3 months, at 6 months
measure: Beck Depression Inventory
timeFrame: baseline, at 3 months, at 6 months
measure: EQ-5D
timeFrame: baseline, at 3 months, at 6 months
measure: Cognitive function
timeFrame: baseline, at 3 months, at 6 months
measure: Cognitive function - CANTAB
timeFrame: baseline, at 3 months, at 6 months
measure: Cerebral blood volume
timeFrame: baseline, at 3 months, at 6 months
measure: Cerebral blood flow
timeFrame: baseline, at 3 months, at 6 months
measure: Fractional anistropy
timeFrame: baseline, at 3 months, at 6 months
measure: Mean diffusivity
timeFrame: baseline, at 3 months, at 6 months
measure: Brain function imaging
timeFrame: baseline, at 3 months, at 6 months
measure: brain function imaging
timeFrame: baseline, at 3 months, at 6 months
measure: Brain network analysis
timeFrame: baseline, at 3 months, at 6 months
measure: Heat/Cold Pain threshold evaluation
timeFrame: baseline, at 3 months, at 6 months
measure: Conditioned pain modulation
timeFrame: baseline, at 3 months, at 6 months
measure: Physical activity
timeFrame: baseline, at 3 months, at 6 months
measure: Exercise capacity
timeFrame: baseline, at 3 months, at 6 months
measure: Inflammatory cytokines
timeFrame: baseline, at 3 months, at 6 months
measure: CD4 number
timeFrame: baseline, at 3 months, at 6 months
measure: CD8 number
timeFrame: baseline, at 3 months, at 6 months
measure: CD4:CD8 ratio
timeFrame: baseline, at 3 months, at 6 months
measure: CD8+CD28null
timeFrame: baseline, at 3 months, at 6 months
measure: Naïve B-Cells number
timeFrame: baseline, at 3 months, at 6 months
measure: CD4CD25 positive number
timeFrame: baseline, at 3 months, at 6 months
measure: Microbiome
timeFrame: baseline, at 3 months, at 6 months
Other outcomes:
Locations:
city: Zerifin
country: Israel
facility: Assaf-Harofeh Medical Center
Study officials:
affiliation: Asaf-Harofhe MC
name: Shai a Efrati, MD
role: PRINCIPAL_INVESTIGATOR
References: