Botox injection into the upper esophageal sphincter in inability to belch: a study comparing botox with placebo.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Algemeen Ziekenhuis Delta

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06], Diseases [C] - Otorhinolaryngologic Diseases [C09]

Trial duration

2 Sep 2024 → ongoing

Decision date (initial)

2024-07-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-512546-42-00

ClinicalTrials.gov

NCT06356025

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

to assess the effect of botulinum toxin injection into the upper esophageal sphincter on the symptoms of ‘inability to belch’ 12 weeks after the injection in a double blind, placebo controlled study.

Secondary objectives 2

1. Secondary objectives include the effect of the treatment on symptoms long term (48 weeks after injection) and safety of the procedure.
2. Exploratory objectives include Improvement in objective measurements using high resolution impedance manometry at week 20, and effect of the treatment on quality of life.

Conditions and MedDRA coding

retrograde cricopharyngeus dysfunction

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures
2. Use of highly effective methods of birth control; defined as those that, alone or in combination, result in low failure rate (i.e., less than 1% per year) when used consistently and correctly; such as implants, injectables, combined oral contraceptives, some IUDs, true sexual abstinence (i.e. refraining from heterosexual intercourse during the entire period of risk associated with the Trial treatment(s)) or commitment to a vasectomised partner.
3. Between 18 and 65 years old
4. Inability to belch, which is bothersome enough to consider treatment*, present for at least 6 months prior to inclusion, and in fulfillment of both categories a and b below:, a. presence of associated gastrointestinal symptoms such as abdominal bloating and discomfort/nausea, flatulence, gurgling noises from the chest or lower neck. b. Absence of other pharyngeal and esophageal pathologies, determined on the basis of history taking and diagnostic tests. * Bothersome = severe enough to impact on usual activities, according to the Rome IV diagnostic criteria
5. Typical findings on high resolution impedance manometry with belch provocation test (10). These typical findings include: No relaxation upon gastroesophageal gas reflux, no air clearance via the UES but instead an increased air presence time include air entrapment and oscillations.

Exclusion criteria 8

1. Participant has a history of surgery in the upper GI tract, that might interfere with the belch reflex (such as anti-reflux surgery)
2. Any disorder, which in the Investigator’s opinion might jeopardise the participant’s safety or compliance with the protocol
3. Any prior or concomitant treatment(s) that might jeopardise the participant’s safety or that would compromise the integrity of the Trial, to be decided at the discretion of the investigator.
4. If applicable: Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate, highly effective contraceptive
5. Participation in another interventional Trial with an investigational medicinal product (IMP) or device
6. >65 years old; < 18 years of age
7. Known hypersensitivity to botulinum toxin type A or to human albumin or sodium chloride.
8. Presence of infection at the proposed injection site(s).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Response to Botox versus placebo, 12 weeks after treatment. We will use the questionnaire of ‘Difficulties with belching’, and response is defined as at least a 50% improvement on question 6A ‘To what extent have the symptoms of 'difficulty burping air' been reduced after treatment?'.

Secondary endpoints 8

1. Response to Botox versus placebo, 48 weeks after treatment. We will use the questionnaire of ‘Difficulties with belching’, and response is defined as at least a 50% improvement on question 6A ‘To what extent have the symptoms of 'difficulty burping air' been reduced after treatment?'.
2. Safety: assessed by the number and type of (serious) adverse events that occurred in each group by week 48, and by the SSQ 1 week and 4 weeks after the procedure.
3. Exploratory: HRQOL using EQ-5D VAS score short-term (1, 4, 12 weeks) and long-term (30 - 48 weeks after the procedure).
4. Exploratory: Patients experience and satisfaction of the treatment based on OTE and OSS short-term (1, 4, 12 weeks after the procedure), and long-term (20 - 48 weeks after the procedure)
5. Exploratory: Evolution of associated gastro-intestinal symptoms short-term (1, 4, 12 weeks) and long-term (20 - 48 weeks after the procedure).
6. Exploratory: Change in objective measurements after, versus before BT injeciton using high resolution impedance manometry at week 20, and comparing with baseline.
7. Exploratory: Improvement in symptoms after Botox versus placebo, 12 and 48 weeks after treatment. We will use the questionnaire of ‘Difficulties with belching’, using a cut-off for improvement of 30% on question 6A ‘To what extent have the symptoms of 'difficulty burping air' been reduced after treatment?'.
8. Exploratory: Safety at week 12, 20 and 48 using SSQ

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Algemeen Ziekenhuis Delta

Sponsor organisation

Algemeen Ziekenhuis Delta

Address

Deltalaan 1

City

Roeselare

Postcode

8800

Country

Belgium

Scientific contact point

Organisation

Algemeen Ziekenhuis Delta

Contact name

K.G. Delsupehe

Public contact point

Organisation

Algemeen Ziekenhuis Delta

Contact name

K.G. Delsupehe

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 20 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications