Clinical trial NCT06356025: Botulinum Toxin Injection in the UES for R-CPD
Official title: Botulinum Toxin Injection in the Upper Esophageal Sphincter for Retrograde-cricopharyngeus Dysfunction: a Prospective, Double Blind, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Retrograde Cricopharyngeus Dysfunction
Lead sponsor: AZ Delta
Sponsor class: OTHER
Collaborators: name: KU Leuven
First posted: 2024-04-10
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of this study is to assess the effect of botulinum toxin injection into the upper esophageal sphincter in a double blind, placebo controlled study. Investigators want to assess the effect on symptoms short term (1-20 weeks after BT injection), and long term (48 weeks after BT injection).

This is a prospective double-blind randomized placebo-controlled study. Questionnaires assessing symptoms will be filled out on several occasions. At 20 weeks, a reassessment of symptoms will be done, without unblinding patients or investigator. Failures (to BT or placebo, defined as no clinical improvement or improvement less than 50%) will get the chance to receive a second procedure with active treatment (BT) in open label.


Eligibility criteria: Participants eligible for inclusion in this Trial must meet all of the following criteria:

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:,

   1. presence of associated gastrointestinal symptoms such as abdominal bloating and discomfort/nausea, flatulence, gurgling noises from the chest or lower neck.
   2. Absence of other pharyngeal and esophageal pathologies, determined on the basis of history taking and diagnostic tests.
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.

   * Bothersome = severe enough to impact on usual activities, according to the Rome IV diagnostic criteria (11, 12).

Participants eligible for this Trial must not meet any of the following criteria:

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. Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential (WOCBP) and not using an adequate, highly effective contraceptive
5. Participation in another interventional Trial with an investigational medicinal product (IMP) or device
6. \&gt;65 years old; \&lt; 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).

Primary outcomes:
measure: Response to Botox versus placebo, 12 weeks after treatment.
timeFrame: week 12
Secondary outcomes:
measure: Response to botox versus placebo 48 weeks after treatment.
timeFrame: 48 weeks
measure: Safety: count of each type of (serious) adverse events in each group
timeFrame: 4 weeks
measure: Safety on swallowing: with SSQ
timeFrame: 4 weeks
Other outcomes:
measure: HRQOL
timeFrame: 1 to 48 weeks
measure: Patients experience and satisfaction of the treatment using overall treatment effect
timeFrame: 1-48 weeks
measure: Patients experience and satisfaction of the treatment using overall symptom severity
timeFrame: 1-48 weeks
measure: Evolution of associated abdominal bloating using a VAS score for symptom severity
timeFrame: 1-48 weeks
measure: Evolution of associated abdominal/thoracic pain using a VAS score for symptom severity
timeFrame: 1-48 weeks
measure: Evolution of associated flatulence using a VAS score for symptom severity
timeFrame: 1-48 weeks
measure: Evolution of associated gurgling noises using a VAS score for symptom severity
timeFrame: 1-48 weeks
measure: Safety during follow-up, with SSQ at week 12, 20 and 48.
timeFrame: 12-48 weeks
measure: Change in objective measurement of UES pressure upon belching during high resolution impedance manometry
timeFrame: 20 weeks
measure: Change in objective measurement of oscillatory movement of air during high resolution impedance manometry
timeFrame: 20 weeks
measure: Improvement of symptoms not reaching primary outcome
timeFrame: 48 weeks
Locations:
city: Roeselare
country: Belgium
facility: AZ Delta
Study officials:
affiliation: AZ Delta
name: Kathelijne G Delsupehe, MD
role: PRINCIPAL_INVESTIGATOR
References: