An Exploratory Evaluation of Biomarkers in Blister Fluid in Healthy Volunteers and Irradiated Skin

NCT00923104 | Completed

• 2 other identifiers: 09012009-C-0120
• Study Type: observational
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

Background:

• Blister fluid contains many of the same biomarkers (substances that can be used to determine the effects of certain kinds of treatments) as blood and urine samples, particularly regarding changes in the skin.
• The Radiation Oncology Branch and others are conducting research studies that require blood and urine samples from healthy volunteers and from patients with cancer. In addition to these samples, researchers would like to collect the fluid from blisters to examine markers of inflammation in the skin. Objectives:
• To compare blood, urine, and blister fluid samples of patients with cancer who are undergoing radiation therapy to that of volunteers without cancer who will not be receiving radiation therapy.
• To gather more information about the effects of radiation therapy on the skin and body fluids of individuals. Eligibility:
• Patients 18 years of age and older who will be receiving radiation therapy for either breast or prostate cancer.
• A separate group of healthy volunteers will also participate in this study. Design:
• Physical examination and blood samples to determine eligibility for the study.
• Blister induction, conducted before the start of radiation treatment, at completion of radiotherapy (last day of treatment), and at a visit 12 months after the end of radiation treatment.
• Blisters will be created through the use of a suction blister device on the hip (for patients with prostate cancer) or on the treated breast or location of removed breast (for patients with breast cancer).
• Blisters will take approximately 30 minutes to form, and fluid will be removed with a needle and syringe.
• Blood and urine samples will also be collected at this time.
• Radiation treatment for breast or prostate cancer will be conducted according to standard procedures, or as directed by a separate research protocol.
• Evaluations during the treatment period:
• Physical examination, including vital signs and body weight checks, and pregnancy test for women who can become pregnant.
• Blood and urine tests.
• Disease evaluation.
• Post-treatment evaluations:
• Clinic visits at months 1, 3, 6, 9, and 12 after the end of radiation therapy for physical examination and disease assessment.
• Study will end 1 year after the final radiation treatment, upon the collection of the final (third) blister fluid sample.

Conditions

Breast Cancer; Healthy Volunteer; Prostate Cancer

Keywords

Radiation; Blister; Healthy Volunteer; Samples; Natural History; Prostate Cancer; Breast Cancer; HV

Outcome Measures

Primary Outcomes (2)

• To determine if cytokine levels in blister fluid change following exposure of the skin to low or high dose radiation

  The primary objectives of this study are (i) to determine if cytokine levels in blister fluid change following exposure of skin to low or high dose radiation, and (ii) to compare cytokine levels in blister fluid from unirradiated skin in normal controls, breast cancer patients, and prostate cancer patients. We will examine IL-1 beta, IL6, TNF-alpha, and MMP-1 and -3 for the primary analysis. The remaining cytokines will be examined in secondary analyses.

  study completion

• To compare blister fluid cytokine levels in blister fluid from unirradiated skin in normal controls, breast cancer patients, and prostate cancer patients

  The primary objectives of this study are (i) to determine if cytokine levels in blister fluid change following exposure of skin to low or high dose radiation, and (ii) to compare cytokine levels in blister fluid from unirradiated skin in normal controls, breast cancer patients, and prostate cancer patients. We will examine IL-1 beta, IL6, TNF-alpha, and MMP-1 and -3 for the primary analysis. The remaining cytokines will be examined in secondary analyses.

  study completion

Secondary Outcomes (6)

• To evaluate the reproducibility of cytokine assays in simultaneously collected blister fluid samples from normal patients.

  study completion

• To determine if there are differences within circulating and skin proteome and cytokine patterns between participants with cancer and healthy normal controls

  study completion

• To determine if cytokine levels and changes at the proteome level measured in blister fluid correlate with absorbed radiation skin dose, acute RTOG skin toxicity (>Grade 3), or late RTOG skin toxicity (>Grade 2).

  study completion

• To determine if changes in the proteome in blister fluid occur following exposure of the skin to low or high dose radiation

  study completion

• To determine how proteomic pattern changes in skin correlate with circulating proteomic patterns.

  study completion

Study Arms (2)

1/healthy volunteers

healthy volunteers

2/patients

subjects with breast cancer, ductal carcinoma in situ, and adenocarcinoma of prostate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients in whom radiotherapy is required for standard management of their breast or prostate cancer. Healthy volunteers with no history of cutaneous inflammatory condition of the skin such as eczema, or psoriasis.@@@@@@

You may qualify if:

• Histological diagnosis: Pathologically confirmed diagnosis of 1) invasive breast cancer, 2) ductal carcinoma in situ, or 3) adenocarcinoma of the prostate.
• Patients in whom the management of the histologic diagnosis will include radiation treatment as part of standard clinical management.
• Patients in whom the extent of disease is considered local or locoregional (i.e. requiring definitive radiotherapy to the breast or prostate).
• Patients must be older than 18 years of age.
• Patients must have a primary medical or surgical oncologist in the community or at NCI who is willing to collaborate with the ROB staff in the clinical management of the patient.
• Patients of childbearing or child- fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while they are being treated with radiotherapy on this study.
• Patients must have an ECOG performance status of 0-2 and a life expectancy greater than 12 months.

You may not qualify if:

• Patients with a history of chronic skin disease such as psoriasis, eczema, or history of keloid formation.
• Patients requiring concurrent use of topical steroids
• Patients requiring concurrent use of glucocorticoid therapy.
• Patients who have received topical or systemic chemotherapy within 4 weeks of enrollment (not including hormonal agents such as antiandrogens, GnRH agonists, aromatase inhibitors, tamoxifen, and similar agents) are excluded.
• Patients requiring concurrent chemotherapy with radiotherapy except as noted in (Protocol section 2.3.1) are excluded.
• Patients with a history of lupus erythematosis, scleroderma, ataxia telengiectasia or other known hypersensitivity to therapeutic radiation.
• Patients with prior radiotherapy to the site which would be used for blister induction.
• Patients who are pregnant because of the potential mutagenic effects of radiation on a developing fetus or newborn.
• Patients with unrelated systemic illness which in the judgment of the Principal Investigator (PI) would compromise the patient s ability to tolerate this therapy or are likely to interfere with the study procedures or results.
• Patients who are in the estimation of the PI, deemed unable or unlikely to adhere to protocol treatment.
• Patients with significant skin atrophy that would interfere with blister formation.
• Breast cancer patients in whom the site of radiotherapy includes a myocutaneous flap or skin graft.
• ELIGIBILITY CRITERIA FOR HEALTHY VOLUNTEERS:
• Healthy volunteers older than 18 years of age.
• Ability to provide informed consent.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• D'Auria L, Pimpinelli F, Ferraro C, D'Ambrogio G, Giacalone B, Bellocci M, Ameglio F. Relationship between theoretical molecular weight and blister fluid/serum ratio of cytokines and five other molecules evaluated in patients with bullous pemphigoid. J Biol Regul Homeost Agents. 1998 Jul-Sep;12(3):76-80.

  PMID: 9795835 BACKGROUND

• Riekki R, Parikka M, Jukkola A, Salo T, Risteli J, Oikarinen A. Increased expression of collagen types I and III in human skin as a consequence of radiotherapy. Arch Dermatol Res. 2002 Jul;294(4):178-84. doi: 10.1007/s00403-002-0306-2. Epub 2002 Apr 27.

  PMID: 12111348 BACKGROUND

• Sonesson B, Rosengren E, Hansson AS, Hansson C. UVB-induced inflammation gives increased d-dopachrome tautomerase activity in blister fluid which correlates with macrophage migration inhibitory factor. Exp Dermatol. 2003 Jun;12(3):278-82. doi: 10.1034/j.1600-0625.2003.120307.x.

  PMID: 12823441 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Breast Neoplasms; Prostatic Neoplasms; Blister

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Skin Diseases, Vesiculobullous; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Study Officials

• Deborah E Citrin, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2009
• First Posted: June 18, 2009
• Study Start: April 23, 2009
• Primary Completion: September 21, 2017
• Study Completion: September 21, 2017
• Last Updated: July 8, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.

Locations

US (1)