Clinical trial NCT02069964: A Prospective Longitudinal Cohort Study Looking at the Difference in Carotid Intima-medial Thickness Between Irradiated and Unirradiated Carotid Arteries in Patients With Head and Neck Cancer
Official title: A Prospective Longitudinal Cohort Study Looking at the Difference in Carotid Intima-medial Thickness Between Irradiated and Unirradiated Carotid Arteries in Patients With Head and Neck Cancer
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Head and Neck Tumours
Lead sponsor: Royal Marsden NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Royal Brompton and Harefield NHS Foundation Trust
First posted: 2014-02-24
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Adult patients with histologically confirmed canceror benign tumours of the head and neck area requiring hemi-neck radiotherapy to ≥ 50Gy

Brief summary: Some patients with head and neck cancer or benign tumours of the head and neck receive radiotherapy to their neck as part of their treatment. The large arteries in the neck, the carotid arteries, are often included in the area being treated with radiotherapy. There is some evidence to show that radiotherapy to these blood vessels can result in thickening and furring of the artery walls some years after treatment. This thickening may then result in stiffening and narrowing of the artery.

Current research is now aimed towards detecting radiotherapy-related changes to the carotid arteries at an earlier stage and towards using new radiotherapy techniques to avoid treating these blood vessels if possible. The question of whether or not the use of preventive medicines like aspirin and cholesterol-lowering tablets helps to reverse this process is currently unanswered.

The aim of this study is to compare the thickness (intima-medial thickness) of the carotid artery wall over time (a period of 5 years) following radiotherapy to the thickness in carotid arteries that have not received radiotherapy. There are many other causes for thickening of arteries (such as high blood pressure, high cholesterol levels and diabetes) and these may affect the ability to measure the effect of radiotherapy change to the artery wall. In order to address this, it is ideal to look at this process in patients who are having only one side of the neck treated and use the other side as a comparison. The study will also be investigating for earlier signs of radiotherapy-related changes, such as stiffening of the artery wall, inflammation in the artery wall (a very early sign of radiotherapy-related change) and some markers in the blood that may indicate that this process is taking place.

The null hypotheses of this study are:

* In irradiated carotid arteries, mean intimal-medial thickness at one year following radiotherapy will be the same as in unirradiated arteries.
* The incidence of carotid artery stenosis will be the same in irradiated and unirradiated carotid arteries
* Arterial wall strain at one year following radiotherapy will be the same in irradiated and unirradiated carotid arteries.
* Microbubble ultrasound will not be able to detect Inflammation in the carotid arteries during radiotherapy as an early marker of atherosclerosis; microbubble ultrasound will not demonstrate at what dose of radiotherapy inflammation begins.
* Serum biomarker levels will not increase over time from baseline after radiotherapy and won't correlate to IMT and arterial strain.


Eligibility criteria: Inclusion Criteria:

* Be 18 years or older
* Histologically confirmed cancer or benign tumours of the head and neck area requiring ≥ 50Gy to one side of the neck (conventional or intensity modulated RT)
* Prior or subsequent neck dissection allowed (irradiated and/or unirradiated side)
* Be able to provide written informed consent

Exclusion Criteria:

* Patients with bulky nodal neck disease that may interfere with acquisition of ultrasound images
* Patients with a prior history of carotid endarterectomy or carotid angioplasty and stenting

Primary outcomes:
measure: The difference in mean carotid IMT at one year after radiotherapy between irradiated and unirradiated carotid arteries.
timeFrame: 1 year
Secondary outcomes:
measure: The difference in mean carotid IMT at 2 and 5 years after radiotherapy between irradiated and unirradiated carotid arteries.
timeFrame: 2 and 5 years
measure: The incidence of carotid artery stenosis in irradiated carotid arteries compared to unirradiated carotid arteries.
timeFrame: 5 years
measure: The difference in carotid arterial wall strain following radiotherapy between irradiated and unirradiated carotid arteries.
timeFrame: 5 years
measure: The difference in arterial wall inflammation between irradiated and unirradiated carotid arteries and dose-related effects
timeFrame: 5 years
measure: The effect of risk-modifying therapy (anti-hypertensives, anti-diabetic medication, HMGCoA reductase inhibitors, smoking cessation) on irradiated and unirradiated carotid arteries.
timeFrame: 5 years
measure: The change in mean serum biomarker levels after radiotherapy.
timeFrame: 1 year
measure: The proportion of patients who develop stroke or TIA.
timeFrame: 5 years
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Royal Marsden Hospital
Study officials:
affiliation: Royal Marsden NHS Foundation Trust
name: Christopher M Nutting, PhD
role: PRINCIPAL_INVESTIGATOR
References: