Clinical trial NCT04340297: Tongjiang Series Prescription Combined With PPIs Descending Ladder Withdrawal in Treating Nonerosive Reflux Disease
Official title: Randomized Double-Blind Clinical Trial of Tongjiang Theory and Syndrome Differentiation Serial Prescriptions Combined With Proton Pump Inhibitors(PPIs)Descending Ladder Withdrawal for the Treatment of Nonerosive Reflux Disease.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Nonerosive Reflux Disease
Keywords: Traditional Chinese medicine
Tongjiang series prescription
Randomized controlled trial
Lead sponsor: Xiyuan Hospital of China Academy of Chinese Medical Sciences
Sponsor class: OTHER
Collaborators: name: Guangdong Provincial Hospital of Traditional Chinese Medicine
name: Wuhan No.1 Hospital
name: The First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine
name: Traditional Chinese Medicine Hospital of KUNSHAN
name: Liuzhou Hospital of Traditional Chinese Medicine
First posted: 2020-04-09
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Nonerosive Reflux Disease (NERD) is a common refractory gastrointestinal disease. Proton Pump Inhibitors (PPIs), the preferred drug, have poor response, single target and poor acid inhibition effect in some patients in clinical application. Long-term use of PPI can lead to many side effects, even dependency. The main Traditional Chinese Medicine (TCM)syndrome types of NERD are liver-stomach depression-heat syndrome, spleen deficiency damp-heat syndrome and cold-heat complicated syndrome. TCM syndrome differentiation treatment has the advantages of overall regulation and individualized treatment. The purpose of this study is to evaluate the safety and efficacy advantages of syndrome differentiation series prescription combined with PPIs descending ladder withdrawal in the treatment of patients who use PPIs for a long time that can not stop, and to solve the problems of multiple side effects and dependency caused by long-term use of PPIs.

Detailed description: Nonerosive Reflux Disease (NERD) accounts for about 70% of Gastroesophageal Reflux Disease (GERD), which is a common refractory gastrointestinal disease. Proton Pump Inhibitors (PPIs), the preferred treatment, have the following problems in clinical use: about 50% of patients respond to PPIs only partially or not at all; PPIs has a single target, and the effect of acid suppression alone is poor; long term use of PPIs can lead to dyspepsia, fundic gland polyp, atrophic gastritis, intestinal flora disorders, and even dependency. Liver-stomach depression-heat syndrome, spleen deficiency damp-heat syndrome and cold-heat complicated syndrome account for 80%-91% of NERD's Traditional Chinese Medicine (TCM) syndrome. TCM syndrome differentiation treatment has the advantages of overall regulation and individualized treatment, but it lacks high-level evidence-based medicine evidence. On the basis of previous work, the project plans to establish sub centers in 6 Chinese hospitals, including 180 patients with NERD who meet the requirements to carry out a multicenter, randomized, double-blind, placebo-controlled clinical study, in which 90 subjects in the experimental group received the treatment of syndrome differentiation series of prescriptions combined with PPIs descending ladder withdrawal, and 90 subjects in the control group received the treatment of placebo combined with PPIs descending ladder withdrawal. The therapeutic effects were evaluated from the following aspects: the VAS score of reflow and heartburn, the rate of discontinuation of antacids, the rate of recurrence of NERD symptoms, the score of TCM syndromes and the improvement of gastrointestinal function. The purpose of this study is to evaluate the efficacy advantage and safety of Tongjiang series prescription combined with PPIs descending ladder withdrawal compared with PPIs descending ladder withdrawal alone for patients who use PPIs for a long time that can not stop, so as to obtain evidence-based medical evidence of high-quality TCM syndrome differentiation treatment of NERD, and form an effective and popularized treatment plan to solve the problems of various side effects and dependency caused by long-term use of PPIs.

Eligibility criteria: Inclusion Criteria:

* 1. It meets the diagnostic criteria of nonerosive reflex disease(NERD)
* 2. Patients with PPIs who are effective for more than 8 weeks and relapse after discontinuation
* 3. Age between 18 and 70 years old
* 4. It meets the diagnostic criteria of liver-stomach depression-heat syndrome, spleen deficiency damp-heat syndrome and cold-heat complicated syndrome of traditional Chinese medicine
* 5. Patients have informed consent and are willing to receive corresponding treatment

Exclusion Criteria:

* 1. Patients with active peptic ulcer, gastrointestinal hemorrhage, severe dysplasia of gastric mucosa or suspected malignant change, achalasia or postoperative achalasia
* 2. There are other organic diseases of the digestive system (such as acute and chronic pancreatitis, cirrhosis, etc.), or systemic diseases that affect the gastrointestinal motility, such as hyperthyroidism, diabetes mellitus over 10 years, chronic renal insufficiency, spirit (the score of SAS and SDS shows severe anxiety or depression), nervous system diseases, etc
* 3. Patients with severe organ diseases such as heart, liver and kidney (such as ALT, AST more than 2 times of normal value), hematopoietic system diseases and tumors
* 4. Pregnant and lactating women
* 5. Patients with history of nervous system disease and mental disease
* 6. People with a history of allergies to all the test drugs
* 7. Subjects who are participating in other clinical trials or have participated in other clinical trials within 4 weeks

Primary outcomes:
measure: Changes of visual analogue (VAS) scores of reflow, heartburn and other major symptoms
timeFrame: 6 weeks during treatment period, 4 weeks during follow-up period
measure: Discontinuation rate of acid inhibitors
timeFrame: 6 weeks of treatment
measure: The change of recurrence rate of main symptoms in Nonerosive Reflux Disease
timeFrame: 6 weeks of treatment, 4 weeks during follow-up period
Secondary outcomes:
measure: Changes in secondary symptom scores
timeFrame: 6 weeks during treatment period, 4 weeks during follow-up period
measure: Changes of Traditional Chinese Medicine syndrome score
timeFrame: Baseline, 2 weeks, 4 weeks and 6 weeks during treatment period, 2 weeks and 4 weeks during follow-up period
measure: Changes of Gastroesophageal Reflux Disease-Health Related Quality of Life (GERD-HRQL) scale scores
timeFrame: Baseline, 2 weeks, 4 weeks and 6 weeks during treatment period, 2 weeks and 4 weeks during follow-up period
measure: The change of the score of chronic gastrointestinal disease patient reported outcome (PRO) scale
timeFrame: Baseline, 2 weeks, 4 weeks and 6 weeks during treatment period, 2 weeks and 4 weeks during follow-up period
measure: The change of Self-rating anxiety scale (SAS) score
timeFrame: Baseline, 2 weeks, 4 weeks and 6 weeks during treatment period, 2 weeks and 4 weeks during follow-up period
measure: The change of Self-rating depression scale (SDS) score
timeFrame: Baseline, 2 weeks, 4 weeks and 6 weeks during treatment period, 2 weeks and 4 weeks during follow-up period
Other outcomes:
Locations:
city: Beijing
country: China
facility: Xiyuan Hospital of China Academy of Chinese Medical Sciences
Study officials:
affiliation: China Academy of Chinese Medical Sciences
name: Xudong Tang, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Li X, Wu H, Zhang B, Chen T, Shi X, Ma J, Zhang J, Tang X, Wang F. Traditional Chinese medicine based on Tongjiang methodology combined with proton pump inhibitor (PPI) step-down in treating non-erosive reflux disease: a study protocol for a multicentered, randomized controlled clinical trial. Trials. 2022 Oct 18;23(1):879. doi: 10.1186/s13063-022-06811-x.