Histamine and Bone Pain Association in Participants With Breast Cancer Metastatic in the Bone

The Role of Histamine in Breast Cancer Bone Pain

This trial studies histamine and bone pain association in participants with breast cancer that has spread to the bone. Studying histamine levels in samples of blood from participants with breast cancer in the laboratory may help doctors learn more about reducing cancer bone pain and preventing further bone metastasis.

Study Overview

• Status: Terminated
• Conditions: Bone Pain; Breast Carcinoma Metastatic in the Bone
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Procedure: Biospecimen Collection

Detailed Description

PRIMARY OBJECTIVES:

I. To correlate levels of histamine in plasma with pain scores in patients with bone metastases from breast cancer that have or have not been treated with palliative radiotherapy.

SECONDARY OBJECTIVES:

I. To perform exploratory studies with additional markers not mentioned, including calcitonin gene-related peptide (CGRP), stem cell factor (SCF), angiotensin II (Ang II) substance P, angiotensin 1-7 (Ang1-7), may be performed at the investigator's discretion.

II. To perform next generation ribonucleic acid (RNA) sequences using the whole blood to determine whether histamine system is involved in the development of cancer-induced bone pain (CIBP).

III. To assess the impact of pain response after radiotherapy on bone structural properties such as bone mineral density and cortical thickness, and patient quality of life, physical and psychological function.

OUTLINE:

Participants undergo collection of blood samples for histamine level analysis via enzyme-linked immunosorbent assay (ELISA).

After completion of study, participants are followed up at 1, 3, and 6 months.

• Study Type: Observational
• Enrollment (Actual): 17

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adults with breast cancer with radiographic evidence of bone metastases

Description

Inclusion Criteria:

• Breast cancer patients with radiographic evidence of bone metastases (by plain film, computed tomography [CT], magnetic resonance imaging [MRI], positron emission tomography [PET] or bone scan) within 8 weeks of registration

  • Weight bearing sites: pelvis (excluding pubis), femur, sacrum and/or sacroiliac joints, tibia, up to 5 consecutive cervical, thoracic or lumbar vertebral bodies, lumbosacral spine
  • Non-weight bearing sites: up to 3 consecutive ribs, humerus, fibula, radius +/- ulna, clavicle, sternum, scapula, pubis
• Patients with and without pain related to the radiographically documented metastases are eligible for study
• Ability to understand and the willingness to sign an Institutional Review Board (IRB)-approved informed consent document

Exclusion Criteria:

• Pregnant women will be excluded

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Ancillary-Correlative (biospecimen collection); Participants undergo collection of blood samples for histamine level analysis via ELISA.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Procedure: Biospecimen Collection; Undergo collection of blood

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma histamine levels	To correlate levels of histamine in plasma with pain scores (3 groups) in patients with bone metastases from breast cancer that have or have not been treated with palliative radiotherapy, analysis of variance (ANOVA) will be used. The histamine levels will be transformed to satisfy the conditional normality assumption if needed. Linear regression models will be used to relate histamine levels (outcome variable) with the pain groups (covariate of interest).	Up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Calcitonin gene-related peptide (CGRP)	Levels of CGRP will be collected. Statistical analysis will correlate CGRP with pain scores (3 groups) in patients with bone metastases from breast cancer that have or have not been treated with palliative radiotherapy, ANOVA will be used.	Up to 6 months
Stem cell factor (SCF)	Levels of SCF will be collected. Statistical analysis will correlate SCF with pain scores (3 groups) in patients with bone metastases from breast cancer that have or have not been treated with palliative radiotherapy, ANOVA will be used.	Up to 6 months
angiotensin II (Ang II) Substance P	Levels of Ang II will be collected. Statistical analysis will correlate Ang II with pain scores (3 groups) in patients with bone metastases from breast cancer that have or have not been treated with palliative radiotherapy, ANOVA will be used.	Up to 6 months
angiotensin 1-7 (Ang1-7) levels	Levels of Ang 1-7 will be collected. Statistical analysis will correlate Ang 1-7 with pain scores (3 groups) in patients with bone metastases from breast cancer that have or have not been treated with palliative radiotherapy, ANOVA will be used.	Up to 6 months
Histamine system involvement	Will perform next generation ribonucleic acid (RNA) sequences using whole blood to determine whether histamine system is involved in the development of cancer-induced bone pain (CIBP).	Up to 6 months
Change in bone structural properties	The thickness of the cortical bone within the irradiated volume will be measured.	Baseline up to 1 month
Change in patient quality of life	The change in patient quality of life will be assessed by the visual analogue scale (VAS) pain scale. The total score range is 0-10 with higher scores denoting worse outcomes.	Baseline up to 1 month
Change in physical and psychological function	To be measured using the EORTC QLQ-BM22 quality of life questionnaire. It's divided into two categories, giving a single value: symptoms and functions. A high score indicates a high level of symptoms and a high level of functioning. The score range is 22-88.	Baseline up to 1 month

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Doris Brown, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2019
• Primary Completion (Actual): September 18, 2024
• Study Completion (Actual): September 18, 2024

Study Registration Dates

• First Submitted: April 10, 2018
• First Submitted That Met QC Criteria: May 7, 2018
• First Posted (Actual): May 18, 2018

Study Record Updates

• Last Update Posted (Actual): August 3, 2026
• Last Update Submitted That Met QC Criteria: July 30, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: IRB00048455; P30CA012197 (U.S. NIH Grant/Contract); NCI-2018-00277 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); CCCWFU 02217 (Other Identifier: Wake Forest University Health Sciences)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No