Expression and Function of the Renin-Angiotensin System in the Esophagus
Status:
Completed
Trial end date:
2012-12-01
Target enrollment:
Participant gender:
Summary
Barrett's esophagus (BE) is the major esophageal pre-neoplastic lesion in which dysplastic
transformations eventually can lead to cancer development. Today, the only way for early
detection of pre-neoplastic lesions is an endoscopic surveillance programme with tissue
sampling for histopathology, the latter being the only validated biomarker for esophageal
adenocarcinoma (EAC)-risk available. New biomarkers are warranted for better patient
selection before inclusion into BE surveillance programmes.
Epidemiologic studies have demonstrated suppressed numbers of cancer prevalence in cohorts
being under different medical treatment. In a British epidemiological study 2007 Sjöberg et
al noted a lower prevalence of EAC among patients treated with antihypertensive drugs
interfering with the renin-angiotensin system (RAS) such as AT1R-blockers and ACE-inhibitors.
The last decade this endocrine signalling system has been proven to be involved in
pathological conditions such as inflammation, wound-healing and even cancer, in several organ
systems.
Earlier reports from the investigators laboratory indicate the existence of a local RAS in
the esophageal wall musculature and in the squamous mucosa. In the investigators latest
explorative study, the investigators discovered the altered expression of "classical" RAS
components in BE with and without dysplasia (unpublished results).
By a possible alteration in RAS-related protein-expression in BE with increasing grade of
dysplasia towards EAC, the investigator may have a possible "pathway" leading to biomarkers
for cancer-development. Furthermore, the already well-known anti-hypertensive drugs
ACE-inhibitors and AT1R-blockers may interfere with the risk of malignancy in BE. The
investigators therefore wish to test, in an exploratory prospective randomized
placebo-controlled setting, whether RAS-related protein-expressions in BE are altered by the
addition of RAS-suppressant pharmaceuticals. In the same manner the investigators wish to see
if the expressions of well-known biomarkers for cancer and inflammation are altered.
Phase:
Early Phase 1
Details
Lead Sponsor:
Göteborg University
Collaborator:
Sahlgrenska University Hospital, Sweden
Treatments:
Angiotensin II Candesartan Candesartan cilexetil Enalapril Enalaprilat