Clinical trial NCT06652724: Relieving Chronic Pain: Psychosomatic Mechanisms and Psychological Interventions in Fibromyalgia and Chronic Headache
Official title: Relieving Chronic Pain: Psychosomatic Mechanisms and Psychological Interventions in Fibromyalgia and Chronic Headache
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Fibromyalgia (FM)
Chronic Migraine Headache
Keywords: fibromyalgia
chronic migraine
fmri
psychology
chronic pain
functional magnetic resonance
psychotherapy
Lead sponsor: University of Roma La Sapienza
Sponsor class: OTHER
Collaborators: name: University of Pavia
name: Azienda Policlinico Umberto I
name: Fondazione Mondino
name: University of Turin, Italy
name: I.R.C.C.S Ospedale Galeazzi-Sant'Ambrogio
First posted: 2024-10-22
Enrollment: 400
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: All participants will be fully aware of the purposes of the research and written informed consent will be obtained from all subjects. All recruited participants will undergo a baseline assessment (T0) using the tests listed in the next section. Patients who meet the inclusion criteria will be enrolled and randomized sequentially into one of three groups: brief psychodynamic therapy (DIT), Expressive Writing Therapy (EST) and controls (TAU). The group selected for the DIT intervention will conduct 16 sessions (one per week) and the group for TSE 8 meetings (one every fortnight) (see description of interventions) for a total intervention time of 4 months.
Primary purpose: TREATMENT

Brief summary: Pain is one of the most important manifestations of the disease state and significantly affects people\&#39;s quality of life. According to the International Association for the Study of Pain (IASP), pain is not only a sensory experience related to the activation of the somato-sensory nervous system, but also an emotional experience, resulting from the cortical and emotional processing of nociceptive signals. This means that perceived pain is the result of a complex interaction between physical sensations and emotional responses.

Pain is classified according to two main criteria: duration and pathophysiological mechanism. In terms of duration, pain can be transient, acute, chronic, or persistent. In terms of pathophysiology, pain can be nociceptive, inflammatory, neuropathic, or nociplastic. The latter, in particular, is characterized by altered nociceptive function, without obvious peripheral damage, and is seen in conditions such as fibromyalgia and chronic migraine.

Chronic pain affects a significant proportion of the population, with estimated prevalence rates between 11% and 40%. According to the US Centers for Disease Control and Prevention, about 20.4 percent of adults suffer from chronic pain. This type of pain is more common in women, people of advanced age, and people with low socioeconomic status. In addition to its physical effects, chronic pain has a major psychological impact, increasing the risk of depression, anxiety, and social isolation. Socially and economically, the costs associated with the treatment and management of chronic pain are high.

Nociplastic pain (DN) refers to a chronic pain state that is not related to visible tissue damage or overt neuropathy, but in which there are alterations in the function of pain sensory pathways. The concept of central sensitization (CS), introduced in the 1990s, describes the amplification of pain signals at the level of the central nervous system, leading to increased sensitivity to pain (hyperalgesia) or pain in response to normally non-painful stimuli (allodynia). This central sensitization has been observed in conditions such as fibromyalgia and chronic migraine.

Fibromyalgia (FM) is a syndrome characterized by widespread musculoskeletal pain associated with fatigue, sleep disturbances, and cognitive deficits. The prevalence of FM is higher among women and tends to be associated with a high level of psychological distress, with anxiety symptoms and depression very common among patients. Although the precise cause of fibromyalgia is still unclear, studies suggest that central sensitization plays a central role in its etiology. Patients with fibromyalgia also have high levels of alexithymia, or the difficulty of identifying and describing emotions, and personality disorders such as avoidant or obsessive-compulsive.

Migraine (CM) affects about 15 percent of the world\&amp;#39;s population and is characterized by severe headache attacks, often associated with nausea, vomiting, and hypersensitivity to light and sound. Chronic migraine occurs when symptoms occur for at least 15 days per month. Several genetic and environmental factors contribute to the development of migraine, and there is growing evidence indicating a bidirectional relationship between migraine and depression. Anxiety and depression are also risk factors for migraine chronification.

The comorbidity between fibromyalgia and chronic migraine has been the subject of numerous studies. About 45%-80% of patients with fibromyalgia also have migraine, while 20%-36% of patients with migraine also have fibromyalgia. This high incidence of comorbidity suggests that there are common pathophysiological mechanisms between the two conditions, probably related to central sensitization and alterations in nociceptive pain pathways. Recent studies have confirmed that patients with both conditions (FibroMig) may have specific psychological and neurofunctional patterns that distinguish them from those with only one of the two diseases.

This study aims to explore the differences between people with fibromyalgia and chronic migraine, with the goal of identifying distinctive psychological and neurofunctional patterns that could help improve treatments for chronic pain management. An innovative aspect of the project is the identification of the FibroMig sub-population, namely those who suffer from both conditions. These patients might exhibit unique neurophysiological and psychological mechanisms that could be used to develop more targeted treatment strategies.

Detailed description: This research project stems from the intention to observe possible differences between people with FM and CM as clinical conditions representative of diagnostic clusters of DN of a chronic nature, with the ultimate goal of helping to improve treatments for pain management (Cohen, 2022).

The overall goals of the project, in line with the literature review showing a dearth of evidence on mechanisms underlying the onset and maintenance of FM and CM and associated subpopulation (FibroMig), is to identify patterns of psychological and neurofunctional functioning associated with these DN syndromes. In light of the elucidation of such processes that can distinguish these clinical populations, the second general purpose will be to evaluate the efficacy of brief psychodynamic treatments in this area, i.e., to test the efficacy of brief psychodynamic treatment on improvement of pain severity, symptoms of chronic pain pathology, mental pain, psychopathological symptoms (anxiety, depression, etc.), effects on alexithymic functioning and quality of life, in three distinct conditions, FM, CM and comorbidities of FM and CM (FibroMig).

Specifically, the project consists of 2 separate studies that aim to:

* To observe possible differences in psychosocial variables among three groups of patients: isolated form (without comorbidities) of FM, CM and FM and CM comorbidities (FibroMig), compared with a group of healthy subjects (HC) (study 1)
* To evaluate possible differences in the organization of baseline brain functioning (resting-state) between the 3 clinical groups and the healthy control sample (study 1)
* To evaluate the effectiveness of dynamic interpersonal psychotherapy (DIT) on the three patient groups (FM, CM and FibroMig) by comparing them with the application of Expressive Writing Therapy (TSE) and a control group (Treatment as usual - TAU) on improvement with respect to pain severity (VAS), symptom severity (FIQR and symptomatology for CM), mental pain (MPQ), psychopathological symptoms related to anxiety and depression (GAD7, HSRD and PHQ6), level of central sensitization (CSI), level of alexithymia (TAS-20) and Quality of Life (SF-12) (Study 2).

Eligibility criteria: Inclusion Criteria:

* minimum age of 18 years;
* at least 5 years of education;
* FM diagnosis according to the criteria reported by Wolfe (2016) for the FM group;
* CM diagnosis according to Olesen (2018) for the CM group;
* medical certification for FM and CM diagnosis for FibroMig group.

Exclusion Criteria:

* severe psychiatric disorders and/or cognitive impairment;
* difficulty understanding/expressing in Italian;
* history of other disorders characterized by chronic pain for FM and CM;
* history of other neurological disorders besides migraine for CM and FibroMig;
* history of other rheumatological disorders besides fibromyalgia for FM and FibroMig;
* For the healthy control group: no diagnosis of FM or CM; no severe psychiatric disorders/cognitive impairment; no or low levels of depression; no history of rheumatological and/or neurological disorders.

Primary outcomes:
measure: severity of pain
timeFrame: An initial survey at the time of enrollment (T0) then one immediately after the end of the planned interventions (T1, after 4 months of the first one) and finally a survey at 6 months of the end of the intervention (T2).
measure: severity of symptoms
timeFrame: An initial survey at the time of enrollment (T0) then one immediately after the end of the planned interventions (T1, after 4 months of the first one) and finally a survey at 6 months of the end of the intervention (T2).
measure: mental pain
timeFrame: An initial survey at the time of enrollment (T0) then one immediately after the end of the planned interventions (T1, after 4 months of the first one) and finally a survey at 6 months of the end of the intervention (T2).
measure: level of central sensitization
timeFrame: An initial survey at the time of enrollment (T0) then one immediately after the end of the planned interventions (T1, after 4 months of the first one) and finally a survey at 6 months of the end of the intervention (T2).
measure: psychopathological symptoms related to anxiety and depression
timeFrame: An initial survey at the time of enrollment (T0) then one immediately after the end of the planned interventions (T1, after 4 months of the first one) and finally a survey at 6 months of the end of the intervention (T2).
measure: alexithymia level
timeFrame: An initial survey at the time of enrollment (T0) then one immediately after the end of the planned interventions (T1, after 4 months of the first one) and finally a survey at 6 months of the end of the intervention (T2).
measure: quality of life
timeFrame: An initial survey at the time of enrollment (T0) then one immediately after the end of the planned interventions (T1, after 4 months of the first one) and finally a survey at 6 months of the end of the intervention (T2).
Secondary outcomes:
measure: traumatic experiences
timeFrame: baseline, pre-intervention
measure: highly sensitivity
timeFrame: baseline, pre-intervention
measure: personality traits
timeFrame: baseline, pre-intervention
measure: defensive functioning
timeFrame: baseline, pre-intervention
measure: psychopathological symptoms
timeFrame: baseline, pre-intervention
measure: reflective function
timeFrame: baseline, pre-intervention
measure: attachment style
timeFrame: baseline, pre-intervention
Other outcomes:
Locations:
city: Rome
country: Italy
facility: Sapienza University of Rome
state: RM
city: Rome
country: Italy
facility: Department of Dynamic and Clinical Psychology and Health Studies
state: RM
Study officials:
affiliation: University of Roma La Sapienza
name: Federica Galli, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Turin, Italy
name: Lorys Castelli, Professor
role: STUDY_DIRECTOR
affiliation: Università di Pavia
name: Sara Bottiroli, Professor
role: STUDY_DIRECTOR
affiliation: University of Milan
name: Piercarlo Sarzi-Puttini, MD, Professor
role: STUDY_DIRECTOR
affiliation: Policlinico Umberto I
name: Cristina Iannuccelli, Dr
role: STUDY_DIRECTOR
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