Bone Pain in Multiple Myeloma- a Translational Study (BPMM)

February 8, 2022 updated by: Sheffield Teaching Hospitals NHS Foundation Trust

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)?

Study Overview

Status

Active, not recruiting

Conditions

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.

Study Type

Observational

Enrollment (Anticipated)

35

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • South Yorkshire
      • Sheffield, South Yorkshire, United Kingdom, S10 2JF
        • Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Study cohort (Confirmed myeloma patients)

Patients with suspected multiple myeloma will be recruited. They will be asked to fill in questionnaires (regarding pain, quality of life, catastrophizing), donate serum samples and allow the research team to access their clinical data and their diagnostic bone biopsy.

Those who receive a positive diagnosis will be followed up upon completion of first-line treatment, and questionnaire data and blood samples collected again.
Control cohort (non-confirmed myeloma patients)

Patients with suspected multiple myeloma will be recruited. They will be asked to fill in questionnaires (regarding pain, quality of life, catastrophizing), donate serum samples and allow the research team to access their clinical data and their diagnostic bone biopsy.

Samples from patients who receive a negative myeloma diagnosis will be used as negative controls.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in bone innervation by immunohistological assessment (presence)
Time Frame: 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.
The presence of sympathetic and sensory nerve fibers innervating the bone will be assessed in the diagnostic trephine bone biopsies.
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.
Change in bone innervation by immunohistological assessment (location)
Time Frame: 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.
The location sympathetic and sensory nerve fibers innervating the bone will be assessed in the diagnostic trephine bone biopsies.
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.
Change in bone innervation by immunohistological assessment (density)
Time Frame: 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.
The density of sympathetic and sensory nerve fibers innervating the bone will be assessed in the diagnostic trephine bone biopsies.
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.
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)
Time Frame: Baseline
Questionnaires will be used to characterize the self-reported experience of pain in patients with firstly-diagnosed myeloma
Baseline
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) )
Time Frame: Baseline
Questionnaires will be used to characterize the quality of life of patients with firstly-diagnosed myeloma
Baseline
Change in quality of life in myeloma after first-line treatment through standardized questionnaires (EORTC QLQ-C30, EORT QLQ-MY20, EORTC QLQ-CIPN20)
Time Frame: 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.
Questionnaires will be used to characterize the quality of life of patients with firstly-diagnosed myeloma and after completion of first-line treatment
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.
Change in pain in myeloma after first-line treatment through standardized questionnaires (BPI, FACT-BP, PCS, painDETECT)
Time Frame: 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.
Questionnaires will be used to characterize the experience of pain in patients with firstly-diagnosed myeloma and after completion of first-line treatment
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in serum bone biomarkers (CTX1, P1NP) measured by ELISA
Time Frame: 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.
Measurement of bone turnover biomarkers in serum samples through enzyme-linked immunosorbent assay (ELISA).
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.
Change in inflammatory serum biomarkers measured by multiplex array.
Time Frame: 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.
Measurement of an set of inflammatory cytokines in serum samples through multiplex cytokine arrays.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sheffield Teaching Hospitals NHS Foundation Trust

Collaborators

University of Copenhagen

Investigators

  • Principal Investigator: Andrew D Chantry, MD, PhD, Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 23, 2019

Primary Completion (Actual)

November 16, 2021

Study Completion (Anticipated)

December 31, 2022

Study Registration Dates

First Submitted

February 6, 2020

First Submitted That Met QC Criteria

February 17, 2020

First Posted (Actual)

February 18, 2020

Study Record Updates

Last Update Posted (Actual)

February 9, 2022

Last Update Submitted That Met QC Criteria

February 8, 2022

Last Verified

February 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STH20993

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Anonymized data will be collected, stored and analyzed. The results of the study will be published in peer-reviewed scientific journals. Individual participant data will not be shared with the scientific or medical community unless specifically requested.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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