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

NCT02879721 | Completed Early Phase 1

• 1 other identifier: 233-09
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

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the investigators discovered the altered expression of "classical" RAS components in BE with and without dysplasia (unpublished results).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

Keywords

Gastrointestinal

Outcome Measures

Primary Outcomes (1)

• Change in expression of proteins associated with inflammation, proliferation and cancer development

  Change in expression of p53, AMACR, Caspase 3, iNOS, VEGFR2, EGFR, CyclinD1, NFkB, PPARy, Cox-2, NLRP3 and MPO after 3 weeks treatment, assessed by Western blot.

  Assessed at baseline (day 0) and after three weeks (day 21) of treatment

Secondary Outcomes (1)

• Change in regulation of potential new biomarkers associated with esophageal cancer

  Assessed at baseline (day 0) and after three weeks (day 21) of treatment

Study Arms (3)

no drug

NO INTERVENTION

No drug and no intervention

AT1R-antagonist

ACTIVE COMPARATOR

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

Drug: Candesartan

ACE-inhibitor

ACTIVE COMPARATOR

Angiotensin converting enzyme inhibitor, (enalapril) 5 mg once daily

Drug: Enalapril

Interventions

Candesartan DRUG

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

Also known as: Atacand, Ratacand, Biopress; CAS 139481-59-7, ATC C09CA06

AT1R-antagonist

Enalapril DRUG

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

Also known as: Vasotec, Enaladex, Renitec; CAS 75847-73-3, ATC C09AA02

ACE-inhibitor

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Barretts esophagus with a minimum length of 1 cm and histomorphologically confirmed low grade dysplasia

You may not qualify if:

• Treatment with ACE-inhibitors (angiotensin converting enzyme inhibitors) or AT1R-antagonists (angiotensin type 1 receptor antagonists). Newly diagnosed or treatment resistant hypertonia or renal failure.

Sponsors & Collaborators

• Göteborg University: lead
• Sahlgrenska University Hospital: collaborator

Study Sites (1)

Dept. of Gastrosurgical Research and Education, Inst. Clinical Sciences, Sahlgrenska University Hospital

Gothenburg, S-41345, Sweden

Location

MeSH Terms

Conditions

Barrett Esophagus

Interventions

candesartan; candesartan cilexetil; Enalapril; Enalaprilat

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Anders F Edebo, MD PhD

  Dept. of Gastrosurgical Research and Education, Inst. Clinical Sciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2016
• First Posted: August 26, 2016
• Study Start: October 1, 2009
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: August 26, 2016

Record last verified: 2016-08

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)