Characterizing Pain in Fibrous Dysplasia of Bone/McCune-Albright Syndrome: an Exploratory Pilot Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 39
- 试验地点
- 1
- 主要终点
- Central sensitization tests, measurement of the Conditioned Pain Modulation (CPM) effect
研究概览
简要总结
Fibrous dysplasia of bone (FD) / McCune-Albright syndrome (MAS) is a rare congenital bone disorder affecting one or multiple bones, caused by a mosaic somatic mutation of the GNAS gene. In some cases, it may be associated with endocrine or cutaneous abnormalities. The spectrum of bone disease is broad, ranging from isolated monostotic fibrous dysplasia to complete skeletal involvement. Functional prognosis can be complex due to pain, bone deformities, and fracture risk. The disease may initially be identified through non-specific clinical signs such as pain. Indeed, bone pain has been reported in up to 81% of adults and 49% of children, mainly affecting the lower limbs and the spine, with highly variable pain intensity that does not always correlate with the extent of bone lesions. This pain may persist throughout life and impact patients' daily activities.
In the general population, it is well known that chronic musculoskeletal pain following events such as surgery or fractures can be associated with central sensitization, a neurophysiological phenomenon characterized by hyperreactivity of the central nervous system, along with impaired modulation of pain through descending inhibitory pathways, a normally protective mechanism that becomes reduced. The pathophysiology of bone pain in FD/MAS remains poorly studied and poorly understood. The presence of central sensitization, reduced pain modulation, and hypersensitivity to everyday stimuli are rarely described but suggested by the existence of chronic pain often lasting many years. The mixed characteristics of pain experienced (nociceptive, neuropathic, inflammatory, or nociplastic) are also poorly defined. To date, no study has explored pain in FD/MAS using a psychophysical approach in comparison with a control population.
Our hypothesis is that patients with FD/MAS exhibit central sensitization with reduced pain modulation. This exploratory pilot study aims to investigate, through psychophysical approaches, the pathophysiological mechanisms underlying pain in FD/MAS.
详细描述
This exploratory pilot study aims to compare central pain sensitization in adults with FD/MAS to that observed in age- and sex-matched healthy volunteers. The primary objective is to assess differences in conditioned pain modulation (CPM), a measure of descending inhibitory pain control and central pain modulation capacity. Secondary objectives include characterization of pain intensity and phenotype, clinical description of FD/MAS manifestations, comparison of thermal and mechanical pain sensitivity thresholds, identification of pain mechanisms (nociceptive, neuropathic, inflammatory, or nociplastic), and comparison of quality of life, sleep quality, anxiety/depression levels, and pain catastrophizing between patients and healthy controls. Blood biomarkers related to bone metabolism will also be compared between groups.
Patients regularly followed in the Rheumatology Department will be informed about the study during routine clinical visits. Patients not requiring regular hospital follow-up may be contacted by their rheumatologist, who will present the study and provide written information. A reflection period of at least seven days will be respected before scheduling the study visit. Participation remains voluntary, and informed consent will be obtained prior to any study procedures.
Healthy volunteers will be preselected from the Clinical Investigation Center volunteer registry and contacted to assess interest in participation. Eligible volunteers will receive study information and will benefit from the same reflection period before inclusion procedures.
Both groups of participants will attend a single visit at the center. During this visit, the objectives and procedures of the study will be explained by the physician. After verification of eligibility criteria and once written informed consent has been obtained, the following assessments will be performed:
- A medical examination and inclusion-related questionnaires (including medical history and clinical characteristics, comorbidities, medication treatments, the WPI and the Kosek nociplastic pain algorithm).
- A blood sample to assess bone biological markers (Fibroblast Growth Factor 23 (FGF23) and C-terminal telopeptides of type I collagen (CTX)).
- A pain assessment including the visual analog scale, the Brief Pain Inventory (BPI), DN4, the PainDetect questionnaire, psychophysical pain assessment (thermal pain thresholds for heat and cold, mechanical pain thresholds, Sudoscan), and evaluation of central sensitization using the conditioned pain modulation (CPM) test, as well as the Pain Catastrophizing Scale (PCS).
- Quality-of-life-related questionnaires including the Pittsburgh Sleep Quality Index (PSQI), the SF-36 quality of life questionnaire, and the Hospital Anxiety and Depression Scale (HADS).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •For patients :
- •Male or female over 18 years of age with fibrous dysplasia/McCune-Albright syndrome diagnosed by a rheumatologist.
- •Mentally and legally able to provide informed consent to participate in the study.
- •Affiliated with a health insurance system.
- •For healthy volunteers :
- •Male or female over 18 years of age.
- •Matched to patients by age and sex.
- •Mentally and legally able to provide informed consent to participate in the study.
- •Affiliated with a health insurance system.
排除标准
- •For patients :
- •Medical and/or surgical history considered by the investigator or delegated physician to be incompatible with study procedures (e.g., amputation or physical limitation preventing completion of pain assessment tests).
- •Recurrent pain at sites planned for stimulation during thermal and mechanical testing (forearms or palms).
- •Presence of anxiety and/or depression defined as Hospital Anxiety and Depression Scale (HADS) score >
- •Use of analgesic medication within the week preceding inclusion.
- •Use of complementary treatments for analgesic purposes (e.g., vitamins, herbal products, cannabinoids).
- •Individuals under legal protection (guardianship or trusteeship) or deprived of liberty.
- •Pregnant or breastfeeding women.
- •Refusal to participate.
- •For heathly volunteers :
- •Medical and/or surgical history considered by the investigator or delegated physician to be incompatible with study procedures (e.g., amputation or physical limitation preventing completion of pain assessment tests).
- •Presence of sleep disorders defined as Pittsburgh Sleep Quality Index (PSQI) score >
- •Presence of anxiety and/or depression defined as HADS score >
- •Use of analgesic medication within the week preceding inclusion.
- •Use of complementary treatments for analgesic purposes (e.g., vitamins, herbal products, cannabinoids).
- •Individuals under legal protection (guardianship or trusteeship) or deprived of liberty.
- •Pregnant or breastfeeding women.
- •Refusal to participate.
研究组 & 干预措施
fibrous dysplasia
干预措施: Visit 1 at the center (Other)
healthy volunteer
Healthy volunteer matched for age and sex
干预措施: Visit 1 at the center (Other)
结局指标
主要结局
Central sensitization tests, measurement of the Conditioned Pain Modulation (CPM) effect
时间窗: Visit 1 / Day 1
The patients are seated, the ATS thermode associated with the Pathway is applied to the dominant forearm. From the baseline value of 32°C, the Pathway delivers a "Pain 60 / Test stimulus" for 10 seconds, and the patient scores the pain on a visual numerical scale from 0 to 100. Then, the Pathway delivers a "Pain 60 / Test stimulus" for 30 seconds, and the patient scores the pain on the same scale. Fifteen minutes after the end of the two stimulations, the patient immersed the non-dominant arm for 60 seconds in a water bath at 46.5°C. Then a second identical sequence of 10 and 30 second stimulations was performed, with the scores recorded after each stimulation on the visual numerical scale from 0 to 100. The CPM effect is measured by taking the difference between the pain scores on the visual numerical scale before and after immersion.
次要结局
- Visual Analog Scale(Visit 1 - Day 1)
- Small fiber neuropathy assessment (Sudoscan®)(Visit 1 - Day 1)
- Dynamic mechanical allodynia(Visit 1 - Day 1)
- The Brief Pain Inventory Questionnaire (BPI)(Visit 1 - Day 1)
- Measurement of the threshold of sensitivity and pain perception induced by a thermal stimulus (hot and cold) at the Pathway - Médoc®(Visit 1 - Day 1)
- Measurement of mechanical pain thresholds and mechanical temporal summation(Visit 1 - Day 1)
- Pain assessment using the Neuropathic Pain Questionnaire (DN4)(Visit 1 - Day 1)
- PainDETECT questionnaire(Visit 1 - Day 1)
- Presence of inflammatory pain(Visit 1 - Day 1)
- Nociplastic pain(Visit 1 - Day 1)
- Clinical characteristics(Visit 1 - Day 1)
- C-terminal telopeptides of collagen type 1 dosage(Visit 1 - Day 1)
- Fibroblast Growth Factor 23 dosage(Visit 1 - Day 1)
- The Pittsburgh Sleep Quality Index (PSQI)(Visit 1 - Day 1)
- The Hospital Anxiety and Depression Scale (HAD)(Visit 1 - Day 1)
- The 36-Item Short Form Survey (SF-36)(Visit 1 - Day 1)
- Pain Catastrophizing Scale (PCS)(Visit 1 - Day 1)