Clinical trial NCT02146495: Targeted Limbic Self-modulation as a Potential Treatment for Patients Suffering From Fibromyalgia
Official title: Mechanistic Perspective on EEG Based Amygdala Driven NF in Fibromyalgia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Fibromyalgia (FM)
Keywords: Fibromyalgia, neurofeedback, fMRI, EEG
Lead sponsor: Tel-Aviv Sourasky Medical Center
Sponsor class: OTHER_GOV
First posted: 2014-05-23
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this study is to test whether voluntary regulation of limbic system activation is possible in patients with fibromyalgia and to examine the neurobehavioral effects of specific neuromodulation of this circuit on somatosensory, limbic, and cognitive processes. This goal will be achieved by using a method previously developed for the construction of an fMRI-enriched EEG model ("EEG-Finger-Print", EFP) that selectively targets the amygdala BOLD activation (Amyg-EFP). The investigators conducted two studies: In the first study, the investigators conducted simultaneous recordings of EEG and fMRI during Amyg-EFP NF training on patients with FM. The main objective is to demonstrate target engagement following Amyg-EFP-NF training in FM patients. In the second study, the investigators aim to conduct a randomized clinical trial to examine the causal effect of the Amyg-EFP NF trial. The investigators will compare neurobehavioral effects between three groups. I. Amyg-EFP-NF group: a multisession NF trial using the Amyg-EFP model. II. Control group 1- sham-NF: a multisession NF trial using sham feedback. III. Control group 2: patients in this group will continue their usual treatment without intervention.

Detailed description: The current study aims to focus on the neural mechanism and brain-guided therapy of Fibromyalgia (FM); a chronic pain syndrome. Despite intense investigations, the pathophysiology of fibromyalgia remains elusive. Several studies demonstrated that morphological and functional changes in the central nervous system may play an important role in FM development and progression. The unknown etiopathology of FM contributed greatly to the absence of mechanism-specific cures. The insufficient treatment for FM, along with the understanding that CNS abnormality constitutes a major factor in FM pathophysiology, emphasizes the need for mechanism-based therapeutic intervention and opens the door for advanced neuromodulation techniques. Guided by this approach, the investigators aspired to establish a multi-function model with the potential to exert neuromodulation effects. To address this goal, the investigators employ a method previously developed for the construction of an fMRI-enriched EEG model ("EEG-Finger-Print", EFP). In this approach, EEG is used to predict specific brain activity, as measured by fMRI in a given region. Our main objective is to explore the neural mechanisms that underlie limbic neuromodulation and to gain a profound understanding of the functional processes that can potentially modify deficient functions in FM. The investigators intend to conduct two studies. In the first study, the investigators focus on the previously developed EFP model that selectively targets the amygdala BOLD activation (Amyg-EFP). The investigators aspired to investigate Amyg-EFP-NF effects on chronic pain in FM. To do so, the investigators conducted simultaneous recordings of EEG and fMRI during Amyg-EFP NF training on patients with FM. The main research objective of this study is to demonstrate target engagement following Amyg-EFP-NF training in FM patients. In the second study, the investigators aim to conduct a randomized clinical trial to examine the causal effect of the Amyg-EFP on patients with FM and to explore the clinical effect of this model on a wide range of symptoms related to FM. To examine the neural, clinical, and behavioral specific effects of the EFP-NF training, the investigators will implement a comprehensive clinical assessment. Furthermore, the investigators will conduct an MRI/fMRI scan before and after the EFP-NF trial, in order to explore the neural modification effects. Clinical follow-up will be conducted after 10-12 months from the post-intervention evaluation. The investigators will compare the neural, clinical, and behavioral effects between three groups. I. Amyg-EFP-NF group: a multisession NF trial using feedback driven by the Amyg-EFP model. II. Control group I- sham-NF: a multisession NF trial using sham feedback. III. Control group II: patients in this group will continue their usual treatment without any intervention. The investigators hypothesize that patients in the Amyg -EFP-NF group will exhibit wider and more robust changes in neural and behavioral outcomes associated with the wide range of symptoms related to FM. This study can significantly advance the understanding of the neural processes that mediate modification of somatic-affective functions in patients with FM and, therefore, enable the establishment of better treatment prediction and possibly more personalized procedures in future studies.

Eligibility criteria: Inclusion Criteria:

* Age: 18-55
* Fibromyalgia diagnosis by a specialist in internal medicine, Neurology or Pain medicine
* Subjective complaints about sleep disorder
* Pain does not stop despite regular medication- at least three events per week of pain ranked five out of ten
* chronic drug treatment should not be change in the near future (6 weeks).
* Hebrew speaker
* Accepted criteria for MRI scan for medical use will be followed, according to the procedures prescribed in the MRI institute of the Tel-Aviv Sourasky medical center.

Exclusion Criteria:

* Non-Hebrew speakers
* Diagnosis of another pain chronic syndrome or any significant medical illness.
* History of psychiatric or neurological diseases requiring hospitalization.

Primary outcomes:
measure: Clinical improvement using the Fibromyalgia Impact Questionnaire (FIQ) to evaluate FM symptoms
timeFrame: Immediately post-intervention relative to the baseline level
measure: Clinical improvement using the Symptom Severity Score (SSS)
timeFrame: Immediately post-intervention relative to the baseline level
measure: Clinical improvement using the Widespread Pain Index (WPI)
timeFrame: Immediately post-intervention relative to the baseline level
measure: Clinical improvement using the SF-36 Health Survey (SF-36) to evaluate daily impacts of FM
timeFrame: Immediately post-intervention relative to the baseline level
measure: Clinical improvement using the Trait Anxiety Inventory (STAI-T) to evaluate the level of anxiety
timeFrame: Immediately post-intervention relative to the baseline level
measure: Clinical improvement using the Beck Depression Inventory (BDI) to evaluate the level of depression
timeFrame: Immediately post-intervention relative to the baseline level
measure: Long-term clinical improvement using the Fibromyalgia Impact Questionnaire (FIQ) to evaluate FM symptoms
timeFrame: Change in symptoms at 10-12 months relative to the baseline level (Follow-up measure vs. Baseline)
measure: Long-term clinical improvement using the Symptom Severity Score (SSS)
timeFrame: Change in symptoms at 10-12 months relative to the baseline level (Follow-up measure vs. Baseline)
measure: Long-term clinical improvement using the Widespread Pain Index (WPI)
timeFrame: Change in symptoms at 10-12 months relative to the baseline level (Follow-up measure vs. Baseline)
measure: Long-term clinical improvement using the SF-36 Health Survey (SF-36) to evaluate daily impacts of FM
timeFrame: Change in symptoms at 10-12 months relative to the baseline level (Follow-up measure vs. Baseline)
measure: Long-term clinical improvement using the Trait Anxiety Inventory (STAI-T) to evaluate the level of anxiety
timeFrame: Change in symptoms at 10-12 months relative to the baseline level (Follow-up measure vs. Baseline)
measure: Long-term clinical improvement using the Beck Depression Inventory (BDI) to evaluate the level of depression
timeFrame: Change in symptoms at 10-12 months relative to the baseline level (Follow-up measure vs. Baseline)
Secondary outcomes:
measure: Neural Prediction
timeFrame: Through study completion, an average of 2 year
Other outcomes:
measure: Brain pattern Changes
timeFrame: Change in neural pattern immediately post-intervention relative to the baseline level (Post-intervention vs. Baseline)
measure: Amyg-EFP-NF regulation success
timeFrame: 1-10 weeks
measure: Pain Assessment
timeFrame: Change in pain level immediately post-intervention relative to the baseline level (Post-intervention vs. Baseline)
measure: Sleep assessment
timeFrame: Change in sleep quality immediately post-intervention relative to the baseline level (Post-intervention vs. Baseline)
Locations:
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
state: N/A = Not Applicable
Study officials:
affiliation: Sagol Brain Institute, Tel Aviv Sourasky Medical Center
name: Ayelet Or-Borichev, PhD
role: PRINCIPAL_INVESTIGATOR
References: