Clinical trial NCT03467438: Efficacy of Zinc L-carnosine in Maintaining Remission of Gastroesophageal Reflux Disease
Official title: Efficacy of Zinc L-carnosine (Hepilor®) in Maintaining Remission of Gastroesophageal Reflux Disease: a Randomised, Double-blind, Placebo-controlled Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Gastroesophageal Reflux Disease
Keywords: heartburn
pyrosis
regurgitation
Lead sponsor: Fondazione IRCCS Policlinico San Matteo di Pavia
Sponsor class: OTHER
First posted: 2018-03-16
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Gastroesophageal reflux disease (GERD), according to the Montreal classification, is defined as a condition that develops when the reflux of stomach contents causes troublesome symptoms and/or complications. GERD, as clinically defined by the presence of heartburn, acid regurgitation, or both, at least once a week, is a global disease, being one of the most common gastroenterological disorders worldwide that affects roughly 10-30% of the general population in the Western world and less than 10% of the Asian populations. GERD complications may be life threatening and range from reflux esophagitis to Barrett's oesophagus and, eventually, adenocarcinoma.

Zinc L-carnosine (brand name in Italy: Hepilor®) is a chelate compound of zinc and L-carnosine, with a long history of more than 20 years of clinical use in Japan that has recently become available in Italy for the treatment of any condition that requires a mucosal protection and mucosal repair within the gastrointestinal tract, thus including GERD. However, clinical data in western countries are limited. The aim of this double-blind, placebo-controlled study is to demonstrate the efficacy of Zinc-l-carnosine in maintaining GERD clinical remission during a 12-week treatment.

Detailed description: The investigators hypothesise that Zinc-l-carnosine is able to maintain GERD remission, thus improving the quality of life of these patients. A comparison with a placebo is necessary, as GERD symptoms may be heavily influenced by the nocebo/placebo effect.

This is a post-marketing, single center, double-blind, and randomized, placebo-controlled, parallel study. Patients with GERD treated with an 8-week cours of proton pump inhibitors will be randomize and receive either Zinc-l-carnosine or placebo for 12-week. GERD symptoms will be assessed with a questionnaire (modified GERD questionnaire by Locke) monthly for 12 weeks and after a 4-week wash-out. Also, quality of life will be assessed at baseline and at 12 weeks with the 36-item short form survey (SF-36).

Eligibility criteria: Inclusion Criteria:

* written informed consent to participate
* be male or female patients ≥ 18 years old, with an established diagnosis of GERD
* have a diagnosis of GERD that is established clinically in case of typical symptoms (heartburn and acid regurgitation ≥ once weekly) or with 24-hour esophageal impedence monitoring in case of atypical symptoms not responsive to proton pump inhibitors (PPIs) or in case of unclear diagnosis
* have been treated with an 8-week course of PPI (as per gold-standard treatment of GERD) before entering the study

Exclusion Criteria:

* any medical condition that requires chronic therapy with PPIs or H2 antagonists; anti-acid agents must be discontinued within the study period
* oesophageal motility disorders
* allergy or intolerance to Hepilor® (it contains parahydroxybenzoate that may cause allergies)

  * inconclusive diagnosis of GERD and related symptoms
  * patients with active H. pylori infection (diagnosed with any of the available tests)
  * previous major oesophageal surgery
  * history of any advanced/relevant organ dysfunction, in particular chronic kidney disease, chronic liver disease of any aetiology, hearth failure
  * any concomitant medical condition with a poor prognosis (\< 3 months)
  * pregnant females
  * inability to conform to the protocol
  * treatment with any investigational drug within the previous 3 months
  * any subject not able to express/understand the informed consent

Primary outcomes:
measure: Gastroesophageal reflux disease (GERD) remission
timeFrame: 4 weeks
measure: Gastroesophageal reflux disease (GERD) remission
timeFrame: 8 weeks
measure: Gastroesophageal reflux disease (GERD) remission
timeFrame: 12 weeks
Secondary outcomes:
measure: 36 item short form health survey
timeFrame: 12 weeks
measure: Sustained GERD remission
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
Study officials:
References:
citation: Vakil N, van Zanten SV, Kahrilas P, Dent J, Jones R; Global Consensus Group. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 2006 Aug;101(8):1900-20; quiz 1943. doi: 10.1111/j.1572-0241.2006.00630.x.
citation: Arakawa T, Satoh H, Nakamura A, Nebiki H, Fukuda T, Sakuma H, Nakamura H, Ishikawa M, Seiki M, Kobayashi K. Effects of zinc L-carnosine on gastric mucosal and cell damage caused by ethanol in rats. Correlation with endogenous prostaglandin E2. Dig Dis Sci. 1990 May;35(5):559-66. doi: 10.1007/BF01540402.
citation: Locke GR 3rd, Talley NJ, Fett SL, Zinsmeister AR, Melton LJ 3rd. Prevalence and clinical spectrum of gastroesophageal reflux: a population-based study in Olmsted County, Minnesota. Gastroenterology. 1997 May;112(5):1448-56. doi: 10.1016/s0016-5085(97)70025-8.
citation: Locke GR, Talley NJ, Weaver AL, Zinsmeister AR. A new questionnaire for gastroesophageal reflux disease. Mayo Clin Proc. 1994 Jun;69(6):539-47. doi: 10.1016/s0025-6196(12)62245-9.