Microvascular Function in Patients Undergoing 5-Fluorouracil Chemotherapy

NCT04042298 | Completed

• 1 other identifier: Pro9646
• Study Type: observational
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

The primary aim of this study is to investigate potential differences in vascular function between patients receiving 5-Fluorouracil (5-FU) chemotherapy, patients receiving chemotherapies other than 5-FU, cancer survivors who were treated with 5-FU, and an age and sex matched control. 5-FU is the third most commonly administered chemotherapeutic agent and its use is associated with the second most occurrences of cardiotoxicity. Despite the known cardiotoxic effects of 5-FU, it's effects on the human vasculature are not well understood. To achieve the goals of this project Laser Doppler flowmetry (LDF) will be used to assess blood flow within the skin microcirculation of the forearm in cancer patients who have received 5-Fluoruracil within the past 30 days (Experimental Group), cancer patients receiving radiotherapy and/or chemotherapy other than 5-Fluorouracil, and an age and sex matched control (Control Group). LDF utilizes a small (\~3 cm) non-invasive sensor placed on the skin. The sensor shines light into the skin, and upon contact with red blood cells (RBCs), the light is reflected and scattered. This information is used to evaluate microvascular blood flow and has previously been used in clinical populations.

Conditions

Gastrointestinal Cancer; Head and Neck Cancer; Breast Cancer; Chemotherapy Effect; 5-Fluorouracil Toxicity

Outcome Measures

Primary Outcomes (2)

• Cutaneous (skin) blood flow (%) following administration of vasoactive substances

  Measured once in each group following administration of vasodilatory (Acetylcholine) and vasoconstrictive (Norepinepherine or Phenylephrine) substances.

  1 day

• Brachial artery flow mediated dilation (FMD)

  Measured once in each group

  1 day

Secondary Outcomes (1)

• Arterial blood pressure

  1 day

Study Arms (4)

5-FU Chemotherapy (Experimental)

Comprised of newly diagnosed cancer patients 21 years or older who have received 5-FU chemotherapy within the past 30 days or are scheduled to receive 5-FU chemotherapy.

Other: Arterial blood pressure; Other: Skin microcirculatory blood flow; Other: Brachial artery blood flow; Other: Venous blood draw

Non-5-FU Chemotherapy (Sub-Control)

Comprised of newly diagnosed cancer patients 21 years or older who have received chemotherapy other than 5-FU within the past 30 days or are scheduled to receive chemotherapy other than 5-FU.

Other: Arterial blood pressure; Other: Skin microcirculatory blood flow; Other: Brachial artery blood flow; Other: Venous blood draw

Age/Sex matched Control (Control)

Age, biological sex, and prior health history (excluding cancer diagnosis) matched control for cancer patients

Other: Arterial blood pressure; Other: Skin microcirculatory blood flow; Other: Brachial artery blood flow; Other: Venous blood draw

5-FU Chemotherapy Cancer Survivor (Survivor)

Cancer survivors who have not received cancer therapy during the past year but previously received 5-Fluorouracil chemotherapy.

Other: Arterial blood pressure; Other: Skin microcirculatory blood flow; Other: Brachial artery blood flow; Other: Venous blood draw

Interventions

Arterial blood pressure OTHER

Measured using an automated non-invasive finger cuff that obtains beat-by-beat blood pressure measurements via finger photoplesmography. Briefly, changes in artery diameter are detected through infrared light in the finger cuff. (Finometer Pro, FMS, The Netherlands).

5-FU Chemotherapy (Experimental); 5-FU Chemotherapy Cancer Survivor (Survivor); Age/Sex matched Control (Control); Non-5-FU Chemotherapy (Sub-Control)

Skin microcirculatory blood flow OTHER

Assessed non-invasively in the forearm skin via Laser Doppler flowmetry in response to locally delivered acetylcholine and norepinepherine or phenylepherine via iontophoresis.

5-FU Chemotherapy (Experimental); 5-FU Chemotherapy Cancer Survivor (Survivor); Age/Sex matched Control (Control); Non-5-FU Chemotherapy (Sub-Control)

Brachial artery blood flow OTHER

A GE Ultrasound System will be used to non-invasively assess brachial artery blood flow prior to and following a standard flow mediated dilation protocol.

5-FU Chemotherapy (Experimental); 5-FU Chemotherapy Cancer Survivor (Survivor); Age/Sex matched Control (Control); Non-5-FU Chemotherapy (Sub-Control)

Venous blood draw OTHER

A venous blood sample from the antecubital vein or a vein in the back of the hand will be taken via venipuncure by a nurse or a certified phlebotomist at the beginning of the experimental visit. These blood samples will be analyzed for the presence of reactive oxygen species and inflammatory markers.

5-FU Chemotherapy (Experimental); 5-FU Chemotherapy Cancer Survivor (Survivor); Age/Sex matched Control (Control); Non-5-FU Chemotherapy (Sub-Control)

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Newly diagnosed cancer patients who have received (or are scheduled to receive) 5-FU chemotherapy within the past 30 days (n=26) will enter the study soon after initiation of treatment. Newly diagnosed cancer patients receiving cancer treatment other than 5-FU (n=26; chemotherapy, radiotherapy, etc.) will enter into the study soon after initiation of treatment. Cancer survivors (n=26) who have previously received 5-FU but not within the year proceeding enrollment will be entered into the study. Age, sex, and health (n=26; excluding cancer) matched controls will be included in the study.

You may qualify if:

• Give voluntary consent to participate in the study
• (Group 1) Current cancer treatment includes 5-FU
• (Group 2) Current cancer treatment does not include 5-FU
• (Group 3) Cancer survivor previously treated with 5-FU but has not received cancer treatment in the year proceeding enrollment.
• (Group 4) Age, sex, and health matched (excluding cancer) control for Group 1

You may not qualify if:

• (Groups 1, 2, and 4) Have received cancer treatment outside of the past year
• Not met above criteria
• Pregnant, breastfeeding, or planning to become pregnant
• Unable to provide informed consent

Sponsors & Collaborators

• Kansas State University: lead

Study Sites (1)

Lafene Health Center

Manhattan, Kansas, 66502, United States

Location

Related Publications (7)

• Yeh ET, Bickford CL. Cardiovascular complications of cancer therapy: incidence, pathogenesis, diagnosis, and management. J Am Coll Cardiol. 2009 Jun 16;53(24):2231-47. doi: 10.1016/j.jacc.2009.02.050.

  PMID: 19520246 BACKGROUND

• Sara JD, Kaur J, Khodadadi R, Rehman M, Lobo R, Chakrabarti S, Herrmann J, Lerman A, Grothey A. 5-fluorouracil and cardiotoxicity: a review. Ther Adv Med Oncol. 2018 Jun 18;10:1758835918780140. doi: 10.1177/1758835918780140. eCollection 2018.

  PMID: 29977352 BACKGROUND

• Taniyama Y, Griendling KK. Reactive oxygen species in the vasculature: molecular and cellular mechanisms. Hypertension. 2003 Dec;42(6):1075-81. doi: 10.1161/01.HYP.0000100443.09293.4F. Epub 2003 Oct 27.

  PMID: 14581295 BACKGROUND

• Polk A, Vistisen K, Vaage-Nilsen M, Nielsen DL. A systematic review of the pathophysiology of 5-fluorouracil-induced cardiotoxicity. BMC Pharmacol Toxicol. 2014 Sep 4;15:47. doi: 10.1186/2050-6511-15-47.

  PMID: 25186061 BACKGROUND

• Luwaert RJ, Descamps O, Majois F, Chaudron JM, Beauduin M. Coronary artery spasm induced by 5-fluorouracil. Eur Heart J. 1991 Mar;12(3):468-70. doi: 10.1093/oxfordjournals.eurheartj.a059919.

  PMID: 2040332 BACKGROUND

• Sudhoff T, Enderle MD, Pahlke M, Petz C, Teschendorf C, Graeven U, Schmiegel W. 5-Fluorouracil induces arterial vasocontractions. Ann Oncol. 2004 Apr;15(4):661-4. doi: 10.1093/annonc/mdh150.

  PMID: 15033676 BACKGROUND

• Sutterfield SL, Caldwell JT, Post HK, Lovoy GM, Banister HR, Ade CJ. Lower cutaneous microvascular reactivity in adult cancer patients receiving chemotherapy. J Appl Physiol (1985). 2018 Oct 1;125(4):1141-1149. doi: 10.1152/japplphysiol.00394.2018. Epub 2018 Aug 9.

  PMID: 30091663 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Venous blood samples (5-7 mL) from the antecubital vein or a vein in the back of the hand will be taken via venipuncure by a nurse or a certified phlebotomist at the beginning of the experimental visit. These blood samples will be analyzed for the presence of reactive oxygen species and inflammatory markers.

MeSH Terms

Conditions

Gastrointestinal Neoplasms; Head and Neck Neoplasms; Breast Neoplasms

Interventions

Arterial Pressure; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Blood Pressure; Hemodynamics; Cardiovascular Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: July 31, 2019
• First Posted: August 1, 2019
• Study Start: June 25, 2019
• Primary Completion: June 1, 2023
• Study Completion: June 1, 2023
• Last Updated: September 2, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)