Clinical trial NCT04273425: Bone Pain in Multiple Myeloma- a Translational Study
Official title: Bone Pain in Multiple Myeloma- a Translational Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Multiple Myeloma
Keywords: Pain
Lead sponsor: Sheffield Teaching Hospitals NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: University of Copenhagen
First posted: 2020-02-18
Enrollment: 35
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients undergoing diagnostic procedures for suspected multiple myeloma at Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital, Sheffield, UK.

Brief summary: While the survival expectancy of myeloma patients continues increasing due to the discovery of novel treatments, bone pain remains one of the main symptoms of this patient population, impairing their mood and quality of life.

The aim of this study is to characterize the subjective experience of pain in myeloma patients, and its correlation with disturbances in serum biomarkers and bone innervation.

Primary research questions:

How is the bone pain experienced by myeloma patients (intensity, location and type of pain) and how does it affect their quality of life?

Do myeloma cells induce changes in the density and/or location of nerve fibres innervating the bone, and if so, are these correlated to the pain experience?

Secondary research questions:

Are the alterations in the bone innervation of myeloma patients similar to those of immunocompetent animal models of the disease (the 5TGM1 model)?

Is serum paraprotein correlated with the subjective experience of myeloma-induced bone pain?

Are the bone turnover biomarkers (C-terminal telopeptides Type 1 collagen, CTX, and procollagen type 1 N-terminal propeptide, P1NP) and inflammatory serum biomarkers correlated with the subjective experience of myeloma-induced bone pain?

Do myeloma cells affect the location, number or density of bone cells (e.g. osteoblasts, osteoclasts)?

Detailed description: Patients undergoing diagnostic procedures (i.e. trephine bone biopsy) for suspected multiple myeloma will be invited to participate in the study, and provided with time to consider their participation.

Patients who consent will be provided with a set of seven standardized questionnaires assessing their pain, quality of life and catastrophizing. Additionally, patients will be asked to fill in demographic information.

Consenting patients will be asked to donate a fasting blood sample and give permission to the research team to retrieve their triphane bone biopsy, once the medical team has finished evaluating it. The presence, location and density of nerve fibres innervating the bone will be evaluated. Patients will also be consented to allow retrieval of medical information from their medical records, and correlations between serum biomarkers, disturbances in bone innervation, paraprotein levels, etc. and their self-reported experience of pain will be investigated. Patients with a negative diagnosis for multiple myeloma (expectably monoclonal gammopathy of undetermined significance (MGUS) patients) will be used as negative controls.

Patients who receive a positive diagnosis for multiple myeloma will be asked to fill in the same set of questionnaires upon completion of the first-line treatment (approximately 7 to 8 months after baseline assessment). Fasting serum blood samples will be collected. To evaluate treatment´s success, it is common medical practice to extract a new trephine bone biopsy upon completion of first line treatment. The research team will access these biopsies and evaluate the presence, density and location of nerve fibres in bone. Changes in nerve fibre profiles, serum biomarkers and the self-reported experience of pain, quality of life and catastrophizing following first-line treatment will be evaluated.

Eligibility criteria: Inclusion Criteria:

* Aged 18 years or older
* Undergoing diagnostic procedures for suspected myeloma (no previous treatment for this)
* Patients who are local to Sheffield (or who are local to any other institute that may join in collaboration)
* Must be able to give informed consent

Exclusion Criteria:

* Patient who are unable to give consent
* Patients who do not speak English
* Patients who are too unwell to be recruited
* Patients who have had recent chemotherapy for different malignancy

Primary outcomes:
measure: Change in bone innervation by immunohistological assessment (presence)
timeFrame: Change from baseline to completion of first line treatment (expected to be measured at 8 months after baseline; expected to be reported within 2 years from baseline) for patients with a positive myeloma diagnosis.
measure: Change in bone innervation by immunohistological assessment (location)
timeFrame: Change from baseline to completion of first line treatment (expected to be measured at 8 months after baseline; expected to be reported within 2 years from baseline) for patients with a positive myeloma diagnosis.
measure: Change in bone innervation by immunohistological assessment (density)
timeFrame: Change from baseline to completion of first line treatment (expected to be measured at 8 months after baseline; expected to be reported within 2 years from baseline) for patients with a positive myeloma diagnosis.
measure: Characterization of pain in patients with firstly-diagnosed myeloma through standardized questionnaires (Brief Pain Inventory (BPI), FACT-BP(FACT-Bone Pain), PCS (Pain catastrophizing scale), painDETECT)
timeFrame: Baseline
measure: Characterization of quality of life in patients with firstly-diagnosed myeloma through standardized questionnaires (EORTC QLQ-C30 (core 30) , EORT QLQ-MY20 (myeloma module 20), EORTC QLQ-CIPN20 (chemotherapy-induced peripheral neuropathy module 20) )
timeFrame: Baseline
measure: Change in quality of life in myeloma after first-line treatment through standardized questionnaires (EORTC QLQ-C30, EORT QLQ-MY20, EORTC QLQ-CIPN20)
timeFrame: Change from baseline to completion of first line treatment (expected to be measured at 8 months after baseline; expected to be reported within 2 years from baseline) for patients with a positive myeloma diagnosis.
measure: Change in pain in myeloma after first-line treatment through standardized questionnaires (BPI, FACT-BP, PCS, painDETECT)
timeFrame: Change from baseline to completion of first line treatment (expected to be measured at 8 months after baseline; expected to be reported within 2 years from baseline) for patients with a positive myeloma diagnosis.
Secondary outcomes:
measure: Change in serum bone biomarkers (CTX1, P1NP) measured by ELISA
timeFrame: Change from baseline to completion of first line treatment (expected to be measured at 8 months after baseline; expected to be reported within 2 years from baseline) for patients with a positive myeloma diagnosis.
measure: Change in inflammatory serum biomarkers measured by multiplex array.
timeFrame: Change from baseline to completion of first line treatment (expected to be measured at 8 months after baseline; expected to be reported within 2 years from baseline) for patients with a positive myeloma diagnosis.
Other outcomes:
Locations:
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital
state: South Yorkshire
Study officials:
affiliation: Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital
name: Andrew D Chantry, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Diaz-delCastillo M, Andrews RE, Mandal A, Andersen TL, Chantry AD, Heegaard AM. Bone Pain in Multiple Myeloma (BPMM)-A Protocol for a Prospective, Longitudinal, Observational Study. Cancers (Basel). 2021 Mar 30;13(7):1596. doi: 10.3390/cancers13071596.