UMIN-ICDS Clinical Trial

Public title

Are changes in salivary secretion after taking vonoprazan linked to treatment-resistant gastroesophageal reflux disease?

Acronym

effect of salivary secretion on reflux symptoms

Scientific Title

Are changes in salivary secretion after taking vonoprazan involved in the pathogenesis of refractory gastroesophageal reflux disease?

Scientific Title:Acronym

effect of salivary secretion on GERD

Region

Japan

Condition

gastroesophageal reflux disease

Classification by specialty

Gastroenterology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

Nearly half of patients with gastroesophageal reflux disease (GERD) do not respond to proton pump inhibitor (PPI) or potassium-competitive acid blocker (PCAB), which is the first-line treatment for GERD, due to factors such as hypersensitivity. We recently reported that the possible pathogenesis of PCAB-refractoriness in nearly 70% of the patients is hypersensitivity. However, there is no established treatment for esophageal hypercreativity.

A decrease in saliva production may be another possible pathogenesis of PPI/PCAB refractoriness since saliva is relevant in neutralizing acid refluxate. Patients with GERD, particularly those with PPI-refractory severe reflux esophagitis, have decreased saliva production. However, the effect of PPI/PCAB on salivary secretion and how it affects reflux pathophysiology remains unclear.

The post-reflux swallow-induced peristaltic wave index (PSPW) was suggested as an indicator of salivary swallow after reflux events on the 24-hour reflux monitoring. The PSPW index increased after PPI treatment in PPI-responsive GERD patients but not in PPI-resistant patients. This suggests that the salivary reflex is impaired even under PPI treatment in PPI-refractory patients. However, the correlation between PSPW and the volume of secreted saliva has not been reported. In addition, it is unclear whether PCAB shows the same effect on salivary secretion as PPI.

We hypothesized that salivary volume increases in the PCAB-responsive group after administration of vonoprazan, a type of PCAB, but not in the PCAB-refractory group and that salivary secretion correlates with PSPW on reflux monitoring. This study aims to (i) investigate changes in salivary secretion after PCAB administration, (ii) compare the difference in the change in salivary secretion after PCAB administration between the PCAB-responsive and refractory groups, and (iii) investigate a correlation between salivary volume and PSPW.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Explanatory

Developmental phase

Primary outcomes

Change in salivary secretion after PCAB administration in PCAB-responsive patients.

Key secondary outcomes

We will investigate the flollowings:
1) change in salivary secretion after PCAB administration in PCAB-refractory patients.
2) correlation between saliva volume and PSPW index
3) correlation between saliva volume and other parameters of reflux monitoring test
4) Whether saliva volume is a predictor of PCAB efficacy. Logistic regression multivariate analysis will be performed using age, gender, and BMI as covariates. If other significant factors are found in the univariate analysis, the covariates will be changed or added.
5) changes in salivary pH and buffering capacity (pH change after acid loading) after PCAB administration.
6) correlation between changes in salivary volume and anxiety/depression, hypervigilance, and sleep scores
7) comparison of changes in salivary pH and buffering capacity between the PCAB responsive and refractory groups.
8) correlation between the symptomatic improvement effect of PCAB and objective GERD diagnosis by endoscopy and reflux monitoring tests.
10) correlation between the degree of mucosal damage at the esophagogastric junction under endoscopy and the objective diagnosis of GERD by reflux monitoring. correlation between the degree of mucosal damage and severity of reflux symptoms.

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Self control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

28day treatment with vonoprazan 20mg

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

18

years-old

<=

Age-upper limit

75

years-old

>=

Gender

Male and Female

Key inclusion criteria

1. 18 <= age <= 75
2. heartburn as a chief complaint
3. total score is 8 or more on the Frequency Scale for the Symptoms of GERD (FSSG)

Key exclusion criteria

1. Take medication that can influence the secretion of saliva, such as antiadrenergic agents and adrenergic alpha-2 agonists, antidepressants, psychotropic drugs, anticholinergic drugs, and smokers in the last two weeks before enrollment.
2. Take medication that affects the secretion of gastric acid, such as PPI, PCAB, and histamine H2 receptor antagonists in the last two weeks before enrollment.
3. Have scleroderma and Sjogren syndrome that can affect esophageal motility and saliva secretion.
4. Have current peptic ulcers.
5. Have an upper gastrointestinal surgery
6. Have severe complications such as heart disease or cancer.
7. Have an allergy to xylocaine.
8. Have an allergy to vonoprazan.
9. pregnant or lactating
10. Have an oral environment in which gum chewing is likely to cause dental problems, such as caries or unstable teeth

Target sample size

50

Name of lead principal investigator

1st name	Yoshimasa
Middle name
Last name	Hoshikawa

Organization

Nippon Medical School Graduate School of Medicine.

Division name

Department of Gastroenterology

Zip code

113-8603

Address

1-1-5 Sendagi Bunkyo-ku Tokyo Japan

TEL

03-3822-2131

Email

y-hoshiikawa@nms.ac.jp

Name of contact person

1st name	Yoshimasa
Middle name
Last name	Hoshikawa

Organization

Nippon Medical School, Graduate School of Medicine.

Division name

Department of Gastroenterology

Zip code

113-8603

Address

1-1-5 Sendagi Bunkyo-ku Tokyo Japan

TEL

03-3822-2131

Homepage URL

Email

y-hoshiikawa@nms.ac.jp

Institute

Nippon Medical School, Graduate School of Medicine.

Institute

Department

Personal name

Organization

Nippon Medical School, Graduate School of Medicine.

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Nippon Medical School, Ethics Committee

Address

1-1-5 Sendagi Bunkyo-ku Tokyo Japan

Tel

03-3822-2131

Email

chuorinri.group@nms.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2024

Year

01

Month

09

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Preinitiation

Date of protocol fixation

2023

Year

12

Month

27

Day

Date of IRB

Anticipated trial start date

2024

Year

01

Month

15

Day

Last follow-up date

2027

Year

03

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2024

Year

01

Month

06

Day

Last modified on

2024

Year

01

Month

06

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000060248