Targeted Limbic Self-modulation as a Potential Treatment for Patients Suffering From Fibromyalgia

NCT ID: NCT02146495

Last Updated: 2024-03-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-31
• Study Completion Date: 2022-08-31

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.

Conditions

Fibromyalgia (FM)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Simultaneous EEG/ fMRI Recordings during Amyg-EFP-NF

Patients with FM will undergo concurrent EEG and fMRI recordings. During the fMRI scans, they will engage in Amyg-EFP NF training.

Group Type: EXPERIMENTAL

Simultaneous EEG and fMRI recordings

Intervention Type: DEVICE

Amyg-EFP-NF Trial

The EFP-NF procedure will include a multisession NF trial (10 sessions) using feedback driven by the Amyg-EFP model.

Group Type: ACTIVE_COMPARATOR

Amygdala-Electrical Fingerprint (Amyg-EFP)-NF Trial

Intervention Type: DEVICE

Neurofeedback training utilizing Amygdala Electrical Fingerprint (Amyg-EFP) methodology

Amyg-EFP-NF Sham Trial

The sham NF procedure will include a multisession NF trial (10 sessions) using sham feedback; in this condition, the feedback will be provided based on a randomized Amyg-EFP signal.

Group Type: SHAM_COMPARATOR

Amygdala-Electrical Fingerprint (Amyg-EFP)-NF Sham Trial

Intervention Type: DEVICE

Sham neurofeedback training based on a randomized artificial Amyg-EFP signal.

Treatment As Usual

Patients in this group will continue their usual treatment without any intervention. Patients in this control group will undergo a complete clinical and neural evaluation at the beginning and end of a defined period, similar to the NF intervention period, and a clinical follow-up (after 10-12 months).

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Simultaneous EEG and fMRI recordings

Intervention Type: DEVICE

Amygdala-Electrical Fingerprint (Amyg-EFP)-NF Trial

Neurofeedback training utilizing Amygdala Electrical Fingerprint (Amyg-EFP) methodology

Intervention Type: DEVICE

Amygdala-Electrical Fingerprint (Amyg-EFP)-NF Sham Trial

Sham neurofeedback training based on a randomized artificial Amyg-EFP signal.

Intervention Type: DEVICE

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tel-Aviv Sourasky Medical Center

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ayelet Or-Borichev, PhD

Role: PRINCIPAL_INVESTIGATOR

Sagol Brain Institute, Tel Aviv Sourasky Medical Center

Locations

Tel Aviv Sourasky Medical Center

Tel Aviv, N/A = Not Applicable, Israel

Countries

Israel

References

Or-Borichev A, Lerner Y, Hamrani Y, Gurevitch G, Mor N, Doron M, Sarna N, Ablin JN, Hendler T, Sharon H. Targeted limbic self-neuromodulation for alleviating central sensitization symptoms in fibromyalgia. BMC Med. 2025 May 28;23(1):304. doi: 10.1186/s12916-025-04138-3.

Reference Type: DERIVED

PMID: 40437546 (View on PubMed)

Other Identifiers

TASMC-14-HS-0044-CTIL

Identifier Type: -

Identifier Source: org_study_id