Pain in Fibrous Dysplasia

• ClinicalTrials.gov Identifier: NCT04125862
• Recruitment Status: Enrolling by invitation
• First Posted: October 14, 2019
• Last Update Posted: September 2, 2021
• Sponsor: Boston Children's Hospital
• Collaborator: National Institutes of Health (NIH)
• Information provided by (Responsible Party): Jaymin Upadhyay, Boston Children's Hospital

Tracking Information

• First Submitted Date: August 12, 2019
• First Posted Date: October 14, 2019
• Last Update Posted Date: September 2, 2021
• Actual Study Start Date: January 5, 2021
• Estimated Primary Completion Date: November 1, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 11, 2019)

% signal difference in BOLD signal [ Time Frame: 50-60 Minutes ]

• % signal difference within striatal and limbic network structures during evoked-heat pain fMRI between FD/MAS patients with pain, FD/MAS patients without pain and matched, healthy volunteers.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 11, 2019)

Numerical clinical pain rating score [ Time Frame: 8 weeks ]

• Numerical clinical pain rating score (NPRS, 0-10 scale) at weeks 0, 1, 4 and 8.

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: October 11, 2019)

18F-FDG or 18F-NaF uptake in FD lesion site [ Time Frame: 15-30 Minutes ]

18F-FDG or 18F-NaF Standard uptake value ratio in FD lesion site

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Pain in Fibrous Dysplasia
• Official Title: Elucidating Mechanisms of Pain in Adolescent and Adult Fibrous Dysplasia Patients
• Brief Summary: Pain remains a common and frequently debilitating symptom, particularly during adulthood of Fibrous Dysplasia/McCune-Albright Syndrome (FD/MAS). For many FD/MAS patients, the amount of pain perceived is not commensurate with the level of detectable musculoskeletal pathology. Using a combination of clinical and biological assessments, this investigation aims to understand what drives pain in FD/MAS.
• Detailed Description: In Fibrous Dysplasia/McCune-Albright Syndrome (FD/MAS), healthy bone tissue and marrow is replaced with pre-osteoblastic, fibrous tissue, yielding skeletal deformities and an increased propensity towards fracture, musculoskeletal weakness and bone pain. Despite the frequent use of pharmacological and non-pharmacological analgesic strategies, pain in FD remains common and frequently debilitating, particularly during adulthood. Moreover, for many patients there is a discordance between perceived pain levels and detectable musculoskeletal pathology. To elucidate the mechanism underlying pain in FD/MAS patients, investigators at the National Institute of Dental and Craniofacial Research (NIDCR), National Center for Complementary and Integrative Heath (NCCIH) and Boston Children's Hospital (BCH) aim to probe three inter-related domains that are projected to underlie pain experience(s) in FD/MAS patients. These include (i.) the presence of maladaptive central nervous system processes that amplify afferent pain or somatosensory signals, and also facilitate persistent pain; (ii.) aberrant interplay between neurological and musculoskeletal systems; (iii.) a mental health status shaped by the overall burden of living with FD and (iv.) the influence of childhood, FD-related complications on adulthood pain phenotypes. To investigate these four domains hypothesized to underlie FD pain as well as inform on the disconnect between pain and FD disease burden, the investigators will employ methods that complement routine clinical evaluation and diagnostic tests (i.e., 18F-NaF PET/CT or 18F-FDG PET/CT) such as neuroimaging, musculoskeletal MRI and such as neuroimaging, musculoskeletal MRI and assessment of inflammatory and pain mediator expression in blood samples.
• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

2 parallel cohorts (FD/MAS patients and matched, healthy controls)

Masking: Single (Participant)
Masking Description:

Individual performing data analyses will be blinded to whether dataset corresponds to FD/MAS patient or matched healthy control

Primary Purpose: Basic Science

• Condition: Fibrous Dysplasia/McCune-Albright Syndrome

Intervention

• Diagnostic Test: MRI-based Neuroimaging
  During evoked pain fMRI, noxious pressure and heat stimuli will be applied in the two anatomical sites noted above. During fMRI data acquisition, a total of 5 pressure stimulations and 5 heat stimulations will be delivered. Both types of pain stimuli will be applied in a 36/17-sec off/on cycle. The off-condition will correspond to a baseline temperature of 35C and the on condition will match the subject-specific and site-specific 7/10 pressure and heat pain thresholds defined during QST procedures. VAS pain ratings associated with evoked pain stimulation will be collected at the end of each scan. The investigators will also explore the structural properties of the CNS by implementing high-resolution anatomical MRI (gray matter volumes) and diffusion tensor imaging (white matter pathway integrity). All CNS imaging will take approximately 50-60 minutes to complete
• Diagnostic Test: Non-contrast MRI
  Musculoskeletal imaging of the affected lower extremity. Patients will be allowed to watch a movie during data acquisition. The following MRI procedures will be completed in order to identify soft tissue lesions in active or painful regions. Fast spin echo (FSE) T2 fat saturated, T1 weighted MRI, FSE proton density MRI, Short-TI Inversion Recovery (STIR), Diffusion weighted MRI (DW-MRI) and 3D Double Echo Steady State (DESS) will be collected. All musculoskeletal MRI will take approximately 30 minutes to complete.
• Diagnostic Test: 18F-FDG-PET/CT
  Data will be collected 30 min after the intravenous administration of 18F-FDG with an expected average dose of approximately 200 MBq. CT data will be collected at a low-dose to minimize radiation exposure. Patients will be positioned supine head-first with arms on the side. The investigators project whole body data to be collected, but in some cases, the field of view may be limited to the patient's skull to below the knees. The data acquisition period is expected to last between 15-30 minutes and total radiation dose will be ~3-4 mSv.
• Diagnostic Test: 18F-NaF-PET/CT
  Data will be collected 30 min after the intravenous administration of 18F-NaF with an expected average dose of approximately 200 MBq. CT data will be collected at a low-dose to minimize radiation exposure. Patients will be positioned supine head-first with arms on the side. The investigators project whole body data to be collected, but in some cases, the field of view may be limited to the patient's skull to below the knees. The data acquisition period is expected to last between 15-30 minutes and total radiation dose will be ~3-4 mSv.

Study Arms

• Fibrous Dysplasia/McCune-Albright Syndrome
  20, Fibrous Dysplasia/McCune-Albright Syndrome Patients with or without pain
  Interventions:

  • Diagnostic Test: MRI-based Neuroimaging
  • Diagnostic Test: Non-contrast MRI
  • Diagnostic Test: 18F-FDG-PET/CT
  • Diagnostic Test: 18F-NaF-PET/CT
• Healthy Controls
  20, matched healthy controls
  Intervention: Diagnostic Test: MRI-based Neuroimaging

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Enrolling by invitation
• Estimated Enrollment (submitted: October 11, 2019): 40
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2022
• Estimated Primary Completion Date: November 1, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria (FD/MAS patients):

• Male and Female subjects
• 10-45 years of age
• English Speaking ability sufficient to comprehend consent (with parental assistance if minor)
• Diagnosis of Fibrous Dysplasia

Exclusion Criteria for patients:

• Younger than 10 or older than 45 years old
• Weight > 285 lbs (weight limit of the MRI table and < 36lbs)
• Surgery leaving implanted material
• Contraindications to MRI scanning and PET scanning (including presence of a cardiac pacemaker or pacemaker wires, metallic particles in the body, vascular clips in the head or previous neurosurgery, prosthetic heart valves, claustrophobia, previous significant research related exposure to ionizing radiation)

Exclusion Criteria for healthy controls:

Same as for the patients, with the addition of the following:

• Use of recreational or illicit drugs History of chronic pain

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 10 Years to 45 Years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04125862
• Other Study ID Numbers: P00030755
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: A two-way material transfer agreement has been executed between collaborating parties (Boston Children's Hospital and NIH)
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Supporting Materials: Analytic Code
• Time Frame: Individual data will start to become available 12/2019 and last for 1.5 years.
• Access Criteria: A two-way material transfer agreement

• Current Responsible Party: Jaymin Upadhyay, Boston Children's Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Boston Children's Hospital
• Original Study Sponsor: Same as current
• Collaborators: National Institutes of Health (NIH)
• Investigators: Not Provided
• PRS Account: Boston Children's Hospital
• Verification Date: September 2021