Effect of Pantoprazole 40mg Daily vs Placebo on Power Spectral Analysis of the Sleep EEG of Patients With GERD.

The Effect Of Pantoprazole 40 mg Once Daily Versus Placebo On The Power Spectral Analysis Of The Sleep Electroencephalogram (EEG) Of Patients With Gastroesophageal Reflux Disease (GERD)

The purpose of this research study is to determine if treatment with pantoprazole 40 mg daily versus a placebo improves sleep quality in patients with gastroesophageal reflux disease (GERD). Another purpose is to determine if treatment with pantoprazole 40 mg once daily versus a placebo improves sleep outcomes in patients with gastroesophageal reflux disease using spectral analysis of sleep electroencephalogram (EEG).

Study Overview

• Status: Completed
• Conditions: Gastroesophageal Reflux Disease
• Intervention / Treatment: Drug: Pantoprazole; Drug: Pantoprazole; Drug: placebo

Detailed Description

It appears that the presence of intraesophageal stimuli alone may not be sufficient to elicit symptoms of heartburn. Most acid reflux events (>80%-90%) do not reach conscious level and thus are not perceived.[3] It is yet to be determined what factors enhance our perception of esophageal stimuli and may help to elevate them to the conscious level. In recent years, central and peripheral factors that may enhance our perception of intraesophageal stimuli have been evaluated. Intraduodenal fat infusion was shown to enhance perception of intraesophageal acid in patients with GERD.[4] This study suggested that fat is an important modulator of postprandial GERD symptoms. Central factors, such as stress and psychological comorbidity, also appear to have an important role in symptom generation in patients with GERD, regardless if esophageal inflammation is present or absent.[5-8] Thus, by modulating brain-gut interactions, perception of pathological and probably physiological events in the esophagus of patients with GERD may be altered.

Poor sleep is a central factor that may enhance perception of intraesophageal stimuli and thus elevate them to the conscious level. Several studies have demonstrated that patients with fibromyalgia or irritable bowel syndrome report increased symptoms due to sleep abnormalities.[9, 10] Similar reports in patients with GERD are not available. A subset of patients with GERD experience nocturnal heartburn that may awaken them during the night. In others, despite lack of nocturnal symptoms, sleep abnormalities may occur due to acid reflux events. In both cases, GERD leads to poor sleep, and that in turn may enhance perception of intraesophageal stimuli, leading to reports of increased frequency and severity of perceived GERD symptoms. Thus, poor sleep may be a crucial factor in symptom generation and exacerbation of patients with GERD.

Recently, we have used a novel technique, power spectral analysis of the sleep electroencephalogram (EEG), to assess patients with heartburn and erosive esophagitis and those with heartburn but without erosive esophagitis.[11] We were able to show that among heartburn patients with GERD, EEG spectral power during sleep is shifted towards higher frequencies as compared to heartburn patients without GERD despite similar sleep architecture.

Several recent therapeutic trials in GERD patients have failed to demonstrate improvement in polysomnographic studies despite improvement in GERD-related symptoms and subjective reports of sleep quality.[12] Spectral analysis of the sleep EEG might be a more sensitive tool than polysomnographic study in assessing objective improvement of sleep in patients receiving antireflux treatment.

In summary, sleep disturbances in patients with GERD are poorly recognized and rarely elicited during clinic visits despite their significant impact on patients' quality of life and probably perception of disease severity. Several studies have demonstrated improvement of subjective reports of sleep quality in patients with GERD receiving antireflux treatment. However, the effect of potent antireflux therapy on objective sleep parameters has yet to be demonstrated.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85723
      • Southern Arizona VA Health Care System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 to 80 yrs of age
• 2 to 3 episodes of GERD/week
• erosive esophagitis or abnormal 24 hr pH
• able to read and understand, complete questionnaires

Exclusion Criteria:

• barrett's esophagus or peptic stricture on endoscopy
• normal EGD and normal 24 hour pH
• previous upper GI surgery
• comorbidity (cardiovascular, respiratory, renal, hepatic)
• use of narcotics or pain medication on regular basis
• insomnia, shift work sleep disorder, sleep apnea, restless leg syndrome
• diabetes, scleroderma or neuromuscular disorders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Pantoprazole; 40 mg once daily for four weeks improves sleep quality in patients with GERD	Drug: Pantoprazole; 40 mg once daily for 4 weeks; Other Names: PPI; Protonix; Drug: Pantoprazole; 40 mg once daily improves sleep quality in patients with GERD.; Other Names: PPI; Protonix
PLACEBO_COMPARATOR: placebo; To determine if treatment with pantoprazole 40 mg once daily vs placebo improves sleep outcome in patients with GERD.	Drug: placebo; 40 mg once daily for 4 weeks; Other Names: sugar pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptom control after 4 weeks of treatment.	To determine if treatment with pantoprazole 40 mg daily vs placebo improves sleep quality in patients with GERD.	April 2008 to July 2010

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of Pantoprazole 40 mg Daily vs Placebo on the Power Spectral Analysis of the Sleep Electroencephalogram of Patients With GERD.	To determine if treatment with pantoprazole 40 mg once daily vs placebo improves sleep outcome in patients with GERD using spectral analysis of sleep electroencephalogram.	April 2008-July 2010

Collaborators and Investigators

• Sponsor: Southern Arizona VA Health Care System
• Investigators: Principal Investigator: Ronnie Fass, MD, Southern VA Health Care System

Publications and helpful links

General Publications

• 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.
• Fass R, Fullerton S, Tung S, Mayer EA. Sleep disturbances in clinic patients with functional bowel disorders. Am J Gastroenterol. 2000 May;95(5):1195-2000. doi: 10.1111/j.1572-0241.2000.02009.x.
• Wiklund IK, Junghard O, Grace E, Talley NJ, Kamm M, Veldhuyzen van Zanten S, Pare P, Chiba N, Leddin DS, Bigard MA, Colin R, Schoenfeld P. Quality of Life in Reflux and Dyspepsia patients. Psychometric documentation of a new disease-specific questionnaire (QOLRAD). Eur J Surg Suppl. 1998;(583):41-9.
• Orr WC, Goodrich S, Robert J. The effect of acid suppression on sleep patterns and sleep-related gastro-oesophageal reflux. Aliment Pharmacol Ther. 2005 Jan 15;21(2):103-8. doi: 10.1111/j.1365-2036.2005.02310.x.
• Netzer NC, Stoohs RA, Netzer CM, Clark K, Strohl KP. Using the Berlin Questionnaire to identify patients at risk for the sleep apnea syndrome. Ann Intern Med. 1999 Oct 5;131(7):485-91. doi: 10.7326/0003-4819-131-7-199910050-00002.
• Goldsmith G, Levin JS. Effect of sleep quality on symptoms of irritable bowel syndrome. Dig Dis Sci. 1993 Oct;38(10):1809-14. doi: 10.1007/BF01296103.

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (ACTUAL): July 1, 2010
• Study Completion (ACTUAL): July 1, 2010

Study Registration Dates

• First Submitted: May 5, 2008
• First Submitted That Met QC Criteria: May 5, 2008
• First Posted (ESTIMATE): May 7, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): August 19, 2010
• Last Update Submitted That Met QC Criteria: August 18, 2010
• Last Verified: August 1, 2010

More Information

Terms related to this study

• Keywords: GERD; heartburn; electroencephalogram; acid reflux; esophagitis; peptic; spectrum analysis
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastroesophageal Reflux; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Pantoprazole
• Other Study ID Numbers: 08-0001-01 & R&D#00-77