Genotype-supported Versus Conventional Proton Pump Inhibitor Dosing

NCT02930824 | Completed Results

• 2 other identifiers: IRB201601774-NU01HG007269
• Study Type: interventional
• Target: 185
• Locations: 1 country
• Sites: 2

Brief Summary

Investigators will conduct a comparative effectiveness study of genotype-supported vs. conventional PPI dosing. Adults and children presenting with Gastroesophageal Reflux Disease (GERD) or dyspepsia symptoms and either 1) being initiated on proton pump inhibitor (PPI) therapy or 2) with continued symptoms on current PPI therapy will be recruited from gastroenterology clinics and randomized to a genotype-supported versus conventional PPI therapy management strategy.

Conditions

Gastroesophageal Reflux Disease

Outcome Measures

Primary Outcomes (5)

• Reflux Disease Questionnaire (RDQ)

  The RDQ was developed to monitor treatment response over time and evaluates 6 symptoms (12 items) covering 3 domains: heartburn, regurgitation, and upper abdominal pain. Each symptom is evaluated using a 6-point Likert scale to assess frequency and severity over the previous week. Each symptom is rated from 1 (did not have) to 6 (severe), and the RDQ mean score is calculated as the mean response to the 12 items. The RDQ mean score thus ranges from 1 to 6 and has been psycho-metrically validated.

  Change from baseline and 12 weeks

• Pediatric Sinonasal Symptom Survey (SN-5)

  The Pediatric Sinonasal Symptom Survey (SN-5) is a validated 5-item scale with each item rated on a scale of worsening symptoms from 1 (none of the time) through 7 (all of the time). Items were averaged to yield a single total score ranging from 1 (better outcomes) to 7 (worse outcomes). The total SN-5 scores were compared between the conventional and genotype-guided dosing groups to determine if one group reported worsening symptoms over the other.

  Week 4 (or next available results)

• Safety Questionnaire (SafetyQ)

  Occurrence of adverse events over the 12 weeks was captured by the Safety Questionnaire (SafetyQ), which was to be completed on a weekly basis by the parents. The Safety Questionnaire (SafetyQ) asked about the presence of seven different respiratory symptoms since their last visit; upper respiratory infection, sore throat, strep throat, bronchitis, pneumonia, ear infection, and acute sinusitis. If a symptom was selected as being present since the last visit, the date of onset and patient-reported explanation of the symptom was recorded. The number of participants who reported infections were compared between each group.

  Over the 12-week period or last date of follow-up

• Gastroesophageal Reflux Disease (GERD) Assessment of Symptoms in Pediatrics Questionnaire (Gasp-Q)

  Gastroesophageal reflux disease (GERD) Assessment of Symptoms in Pediatrics Questionnaire (Gasp-Q) is a validated patient-reported outcome questionnaire that evaluated proton pump inhibitor therapy efficacy. Gasp-Q inquired about the severity and frequency of belly pain, chest pain, difficulty swallowing, choking, burping, nausea, pain after eating, night pain, and vomiting. If the symptom was present, the patient was asked to score the severity of the symptom ranging from 1 (Not at all severe) to 7 (Most severe). A composite score was then calculated based on the scoring of the 9 symptoms and ranged from 9 to 63.

  Change in score from baseline to the week 4 ± 1-week

• Pediatric Quality of Life Inventory (PedsQL) Gastrointestinal Symptoms Module

  Pediatric Quality of Life Inventory (PedsQL) Gastrointestinal Symptoms Module is a validated patient-reported outcome questionnaire and Likert response scale, to evaluate proton pump inhibitor therapy efficacy. The gastrointestinal problems included in the PedsQL were stomach pain and hurt, stomach upset, food and drink limits, trouble swallowing, heartburn and reflux, gas and bloating, constipation, diarrhea, and worry. Participants were asked to rate the symptoms from 0 (never a problem) to 4 (almost always a problem).

  Change in score from baseline to the week 4 ± 1-week

Study Arms (4)

Adult Genotype guided treatment

EXPERIMENTAL

For adults randomized to the genotype-supported arm a CYP2C19 genotype will be provided to physicians to assist in dosing.

Genetic: CYP2C19 genotyping

Adult Conventional treatment

NO INTERVENTION

For adults randomized to the conventional arm no genotype will be provided to physicians to assist in dosing.

Pediatric Genotype guided treatment

EXPERIMENTAL

For children randomized to the genotype-supported arm a CYP2C19 genotype will be provided to physicians to assist in dosing.

Genetic: CYP2C19 genotyping

Pediatric Conventional treatment

NO INTERVENTION

For children randomized to the conventional arm no genotype will be provided to physicians to assist in dosing.

Interventions

CYP2C19 genotyping GENETIC

All proton pump inhibitors are metabolized in part by the CYP2C19 enzyme, which is encoded by the highly polymorphic CYP2C19 gene. Based on variations within this gene the effectiveness of the drug may be reduced.

Adult Genotype guided treatment; Pediatric Genotype guided treatment

Eligibility Criteria

• Age: 5 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age
• diagnosed with GERD or any other stomach acid mediated condition for which a PPI treatment is provided
• currently under a Proton Pump Inhibitor (PPI) therapy or will start a PPI therapy
• Parents/legal guardians and or child must have access to internet and a valid email address

You may not qualify if:

• history of extensive esophageal or gastric surgery
• diagnosed with any major chronic illness or conditions that in the opinion of the gastroenterologist that would interfere with participation in the study
• history of Phenylketonuria (PKU) and patients with a history of previous adverse effects from PPI treatment or sensitivity to aspartame (NutraSweet, Equal)
• Adult:
• years of age or older
• Gastroesophageal Reflux Disease symptoms
• Being initiated on PPI therapy OR continues to have symptoms despite PPI therapy
• Extensive esophageal or gastric surgery
• Any chronic illness that would interfere with the study

Sponsors & Collaborators

• University of Florida: lead
• Nemours Children's Hospital: collaborator
• National Human Genome Research Institute (NHGRI): collaborator

Study Sites (2)

University of Florida

Gainesville, Florida, 32610, United States

Location

Nemours Children's Hospital

Orlando, Florida, 32827, United States

Location

MeSH Terms

Conditions

Gastroesophageal Reflux

Condition Hierarchy (Ancestors)

Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Limitations and Caveats

Pilot study with small sample size and endpoints analyzed in RM/UM subset; no pharmacokinetic analyses done; pragmatic design where any PPI medication could be prescribed; did not account for over-the-counter antacid medications

Results Point of Contact

• Title: Dr. Larisa Cavallari
• Organization: University of Florida

LCavallari@cop.ufl.edu

(352) 273-8245

Study Officials

• Larisa Cavallari, PharmD

  University of Florida

  PRINCIPAL INVESTIGATOR

• James P Franciosi, MD

  Nemours Children's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2016
• First Posted: October 12, 2016
• Study Start: December 1, 2016
• Primary Completion: July 17, 2019
• Study Completion: July 17, 2019
• Last Updated: May 16, 2024
• Results First Posted: June 21, 2021

Record last verified: 2024-05

Locations

US (2)