Expression and Function of the Renin-Angiotensin System in the Esophagus

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the investigators discovered the altered expression of "classical" RAS components in BE with and without dysplasia (unpublished results).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.

Conditions

• Barrett's Esophagus

Interventions

DRUG

Candesartan

Angiotensin II, type 1 receptor inhibitor, (candesartan) 8 mg once daily for

DRUG

Enalapril

Angiotensin-converting enzyme (ACE) inhibitor (enalapril) 5 mg once daily

Sponsors & Collaborators

• Sahlgrenska University Hospital

  collaborator OTHER

• Göteborg University

  lead OTHER

Principal Investigators

• Anders F Edebo, MD PhD · Dept. of Gastrosurgical Research and Education, Inst. Clinical Sciences

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

20 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2009-10-31

Primary Completion

2012-12-31

Completion

2012-12-31

Countries

• Sweden

Study Locations