Buspirone for weak or absent esophageal peristalsis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

UZ Leuven

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

10 Sep 2019 → 17 Mar 2026

Decision date (initial)

2024-10-24

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-516667-91-00

EudraCT number

2019-002182-35

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

To investigate the effect of buspirone on high-resolution manometry parameters (specifically: distal contractile integral, DCI) in patients with poor esophageal motility during a high resolution impedance manometry with 3 types of boluses (on liquid bolus, 5mL, in supine position)

Secondary objectives 3

1. • To investigate the effect of buspirone vs. placebo on several esophageal and EGJ pressure flow parameters (PCI es., DCI, Largest Break Size, DL, IRP4s, PFI, IR, DPA, DPE, RP, CSI, BPT, BFT, EGJ Rest.P, EGJCI, LES-CD) as measured by high resolution impedance manometry
2. • To investigate the influence of buspirone on changes in symptoms using the validated Mayo Dysphagia Questionnaire
3. • To investigate the influence of buspirone on changes in overall treatment evaluation (OTE) and overall symptom severity (OSS)

Conditions and MedDRA coding

ineffective motility or absent peristalsis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Ineffective motility or absent contractility identified on HRiM
2. Primary complaint of dysphagia for a minimum of 2 months
3. Age > 18 years
4. No anatomical cause for symptoms
5. No hiatal hernia ≥3 cm
6. 5. Sexually active women of childbearing potential participating in the study must be using an appropriate form of contraception.

Exclusion criteria 14

1. Endoscopic signs of severe erosive esophagitis (grade C or D, Los Angeles classification) on endoscopy performed off PPI treatment in the 12 months prior to screening, or ≥ grade B when endoscopy is performed during PPI treatment.
2. Systemic diseases, known to affect esophageal motility (i.e. systemic sclerosis)
3. Surgery in the thorax or in the upper part of the abdomen (appendectomy and cholecystectomy are allowed).
4. Hiatal hernia ≥3 cm
5. QT c>450 ms.
6. Use of medication that effect cholinergic function such as anticholinergics, tricyclic antidepressants.
7. Concomitant promotility agents such as prucalopride or domperidone.
8. Concomitant use of more than one benzodiazepine.
9. Significant neurological, respiratory, hepatic, renal, hematological, cardiovascular, metabolic or gastrointestinal cerebrovascular disease as judged by the investigator.
10. Major psychiatric disorder.
11. Pregnancy or breastfeeding.
12. History of poor compliance.
13. History of/or current psychiatric illness that would interfere with ability to comply with protocol requirements or give informed consent.
14. History of alcohol or drug abuse that would interfere with ability to comply with protocol requirements.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in distal contractile integral (DCI, mm Hg*s*cm) between buspirone and placebo established on high resolution impedance manometry (HRiM), for the liquid bolus (5 mL) in supine position.

Secondary endpoints 20

1. Change in symptoms between placebo and buspirone during the HRiM with 3 types of boluses: A Likert score applied during all swallows: 1 (Normal), 2 (Slow passage of bolus), 3 (Stepwise passage), 4 (Partial Blockage), 5 (Complete Blockage)
2. Proximal Contractile Integral (PCI es., mmHg.s.cm)
3. Distal Contractile Integral (DCI, mmHg.s.cm)
4. Largest Break Size (cm)
5. Distal Latency (DL, s)
6. Integrated Relaxation Pressure 4s (IRP4s, mmHg)
7. Pressure Flow Index (PFI)
8. Impedance Ratio (IR)
9. Distension Pressure Accommodation (DPA, mmHg)
10. Distension Pressure Emptying (DPE, mmHg)
11. Ramp Pressure (RP, mmHg/s)
12. Contractile Segment Impedance (CSI, Ohms)
13. Bolus Presence Time (BPT, s)
14. Bolus Flow Time (BFT, s)
15. Esophago-Gastric Junction Resting Pressure (EGJ Rest.P, mmHg)
16. Esophago-Gastric Junction Contractile Integral (EGJCI, mmHg.cm)
17. Lower Esophageal Sphincter – Crural Diaphragm (LES-CD, mm)
18. Mayo Dysphagia Questionnaire
19. Overall Treatment Evaluation
20. Overall Symptom Severity

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

UZ Leuven

Sponsor organisation

UZ Leuven

Address

Herestraat 49

City

Leuven

Postcode

3000

Country

Belgium

Scientific contact point

Organisation

UZ Leuven

Contact name

Jan Tack

Public contact point

Organisation

UZ Leuven

Contact name

Jan Tack

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 4 files

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

Application history

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