Nutcracker OesophagusPhase 2TIBOHNCT01955174
Botulinum Toxin Injection in Hypercontractile Esophagus
A Phase 2 study testing Esophageal endoscopic injection of botulinum toxin and No injection of botulinum toxin in people with Nutcracker Oesophagus, run by Hospices Civils de Lyon at 2 sites in France.
Trial summary
This study aims to evaluate the efficacy and the safety of endoscopic injection of 100 IU of botulinum toxin (BTX) in the distal esophagus in patients with symptoms related to hypercontractile esophageal motility disorders. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Nutcracker Oesophagus
- What is being tested?
- Esophageal endoscopic injection of botulinum toxin and No injection of botulinum toxin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 2 sitesFrance
- Study dates
- Aug 2013to Feb 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient with non-cardiac chest pain and/or dysphagia with global Eckardt score strictly above 3 points or equal to 3 only for " chest pain " or " dysphagia " - Hypercontractile esophagus with normal esogastric junction relaxation based on the Chicago classification in high resolution manometry
- Man or woman 18-year old or older
- Normal upper gastrointestinal endoscopy within one year before inclusion
- Barium swallow without argument for external compression
- Effective form of birth control (if applicable)
- Signed written informed consent form voluntarily
- Patient with health insurance
Who cannot join
- Man or woman under 18-year old
- Past history of eso-gastric surgery
- Evolutive cancer or coagulation disorders
- Absence of effective form of birth control (if applicable)
- Pregnant woman or woman who plans to become pregnant during the expected length of the study
- Breastfeeding woman
Show all 17Show fewer
- Allergy to botulinum toxin or excipients
- Myasthenia
- Aminoglycoside treatment
- Endoscopic contraindication prior to the study
- Endoscopic contraindication during the study
- Psychiatric or addictive disease which could affect compliance to the constraints of the study
- Patient refusing to participate to the study
- Language barrier limiting the understanding of the study
- Incapability to give consent
- Concomitant participation to another research study
- No written consent form
Trial locations and contacts
2 sites in 1 country.
France2 sites
Service d'Hépato-Gastro-Entérologie et Oncologie Digestive- Hôpital Haut Lévêque - CHU de Bordeaux
Bordeaux, 33075
Service d'Exploration Fonctionnelle Digestive - Hôpital Edouard Herriot Pavillon H 5 - Hospices Civils de Lyon
Lyon, 69437
About this study
Official title: Endoscopic Injection of Botulinum Toxin in Patients With Hypercontractile Esophageal Motility Disorders: a Prospective, Randomized, Double-blind, Controlled Study
This study aims to evaluate the efficacy and the safety of endoscopic injection of 100 IU of botulinum toxin (BTX) in the distal esophagus in patients with symptoms related to hypercontractile esophageal motility disorders.
Read the detailed description
Eligible patients will present chest pain and/or dysphagia related to the following hypercontractile esophageal motility disorders: distal esophageal spasm, jackhammer esophagus, nutcracker esophagus or type III achalasia with normalization of the integrated relaxation pressure after treatment, based on the Chicago classification of esophageal motility disorders for high resolution manometry (HRM). Upper gastrointestinal endoscopy and barium swallow will be performed before BTX injection to eliminate secondary disorders.
This is a prospective, randomized, double blind, controlled trial comparing BTX injection to sham procedure (absence of injection, the clinical team performing the follow-up will not be aware of the result of the randomization).
Drugs which could affect esophageal motility (nitrates and calcium channel blockers) will be stopped during the study.
Included patients will undergo esophageal endoscopic ultrasound examination (EEUS) and upper gastrointestinal endoscopy under general anesthesia. In absence of contraindications, patients will be randomized in two arms: BTX injection or no injection. The active treatment group will receive 100 units of type A BTX (Botox®, Allergan) diluted in 10 mL of saline serum; BTX will be injected into the lower third of the esophageal wall in 10 sites between 2 and 10 cm above the squamo-columnar junction. The control arm will receive no injection after the EEUS and upper GI endoscopy (sham procedure).
Clinical response will be assessed based on the evolution of the Eckardt score, a quality of life score (Gastrointestinal Quality of Life Index (GIQLI), and weight gain. A significant clinical response will be defined as an Eckardt score < 3 (together with individual scores < 2). Manometry patterns will be compared before and after the procedure. Safety will be monitored based on the occurrence of chest pain scored on a Likert scale and occurrence of adverse events.
Follow-up clinical evaluation will be performed 1 and 2 months after the procedure. A second esophageal HRM will be realized 3 months after the procedure, followed by endoscopic BTX injection in case of non-response and two monthly visits.
Follow-up visits will be done 6 and 12 months after the first procedure. An additional HRM will be performed at 12 months.
- Conditions
- Nutcracker Oesophagus
- Being tested
- Esophageal endoscopic injection of botulinum toxin, No injection of botulinum toxin
- Keywords
- Botulinum toxin, Esophageal motility disorder, Distal esophageal spasm
- Medical subject headings
- Esophageal Motility Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Esophageal endoscopic injection of botulinum toxinDrug
Endoscopic injection of botulinum toxin in the esophageal muscle : one hundred units of type A botulinum toxin (Botox®, Allergan) diluted in 10 mL of normal saline and injected at the lower third of the esophageal wall in 10 sites between 2 and 10 cm above the Z-line.
No injection of botulinum toxinOther
Upper gastro-intestinal endoscopy without any injection
| Study group | Role | What they receive |
|---|---|---|
| Botulinum toxin injection | Experimental | Esophageal endoscopic injection of botulinum toxin Receives: Drug: Esophageal endoscopic injection of botulinum toxin |
| No injection | Sham comparator | No injection of botulinum toxin Receives: Other: No injection of botulinum toxin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical response
Determination of the percentage of patients with clinical response defined by a global Eckardt score <3 and individual subscores <2
Measured: 3 months after Botulinum toxin injection or sham procedure
Secondary outcomes (7)
Clinical symptoms improvement
Determination of the percentage of patients with clinical response defined by a global Eckardt score <3 and individual subscores <2
Measured: 12 months after Botulinum toxin injection or sham procedure
Clinical symptoms improvement
Determination of the percentage of patients with clinical response defined by a global Eckardt score <3 and individual subscores <2
Measured: After 2 procedures of Botulinum toxin injection or sham procedure
Safety
Evaluation of chest pain with numerical scale from 0 (no pain) to 10 (worst pain) along the 15 days following the procedure, and percentage of patients experimenting adverse events.
Measured: Days 1- 7 after procedure. Month 1,3, 4, 6 and 12 after procedure
Quality of life improvement
Evaluation of the quality of life with the Gastrointestinal Quality of Life Index (GIQLI)
Measured: At the first visit, 3 months, 6 months and 12 months after the first therapeutic procedure (botulinum toxin injection or sham procedure)
Weight gain
Evaluation of weight in kg
Measured: 3 months, 6 months and 12 months after the first therapeutic procedure (botulinum toxin injection or sham procedure)
Modification of HRM pattern
Change towards normal of specific HRM metrics: decrease of mean Distal Contratile Integral, disappearance of contraction with DCI > 8 000, increase of the % of contractions with normal Distal Latency
Measured: 3 and 12 months after the first procedure (botulinum toxin injection or sham procedure)
Clinical and paraclinical characteristics of responders versus non-responders
Age, sex, BMI, associated diseases, esophageal motility disorder according to the Chicago classification, associated medications, severity of symptoms at baseline (Eckardt) score, impairment of QOL at baseline (GIQLI score)
Measured: 12 months after the first therapeutic procedure (botulinum toxin injection or sham procedure)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2013 (estimated)
- Study startAug 2013
- Primary completionMay 2017
- Study completionFeb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Nutcracker OesophagusStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- François MION, MD, Principal investigator, Hospices Civils de Lyon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01955174
- Sponsor's protocol ID
- 2012.779
- Acronym
- TIBOH
- Status last verified
- Dec 2025
- First submitted
- 27 Sep 2013
- Last updated
- 19 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Mion F, Marjoux S, Subtil F, Pioche M, Rivory J, Roman S, Zerbib F. Botulinum toxin for the treatment of hypercontractile esophagus: Results of a double-blind randomized sham-controlled study. Neurogastroenterol Motil. 2019 May;31(5):e13587. doi: 10.1111/nmo.13587. Epub 2019 Apr 11.
PubMed 30974039
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Endoscopic Injection of Botulinum Toxin in Patients With Hypercontractile Esophageal Motility Disorders: a Prospective, Randomized, Double-blind, Controlled Study
- ClinicalTrials.gov ID
- NCT01955174
- Acronym / sponsor ID
- TIBOH / 2012.779
- Conditions
- Nutcracker Oesophagus
- Keywords
- Botulinum toxin, Esophageal motility disorder, Distal esophageal spasm
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- Aug 2013 (actual)
- Primary completion
- May 2017 (actual)
- Study completion
- Feb 2018 (actual)
- First posted
- 7 Oct 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study aims to evaluate the efficacy and the safety of endoscopic injection of 100 IU of botulinum toxin (BTX) in the distal esophagus in patients with symptoms related to hypercontractile esophageal motility disorders.
Detailed description
Eligible patients will present chest pain and/or dysphagia related to the following hypercontractile esophageal motility disorders: distal esophageal spasm, jackhammer esophagus, nutcracker esophagus or type III achalasia with normalization of the integrated relaxation pressure after treatment, based on the Chicago classification of esophageal motility disorders for high resolution manometry (HRM). Upper gastrointestinal endoscopy and barium swallow will be performed before BTX injection to eliminate secondary disorders.
This is a prospective, randomized, double blind, controlled trial comparing BTX injection to sham procedure (absence of injection, the clinical team performing the follow-up will not be aware of the result of the randomization).
Drugs which could affect esophageal motility (nitrates and calcium channel blockers) will be stopped during the study.
Included patients will undergo esophageal endoscopic ultrasound examination (EEUS) and upper gastrointestinal endoscopy under general anesthesia. In absence of contraindications, patients will be randomized in two arms: BTX injection or no injection. The active treatment group will receive 100 units of type A BTX (Botox®, Allergan) diluted in 10 mL of saline serum; BTX will be injected into the lower third of the esophageal wall in 10 sites between 2 and 10 cm above the squamo-columnar junction. The control arm will receive no injection after the EEUS and upper GI endoscopy (sham procedure).
Clinical response will be assessed based on the evolution of the Eckardt score, a quality of life score (Gastrointestinal Quality of Life Index (GIQLI), and weight gain. A significant clinical response will be defined as an Eckardt score < 3 (together with individual scores < 2). Manometry patterns will be compared before and after the procedure. Safety will be monitored based on the occurrence of chest pain scored on a Likert scale and occurrence of adverse events.
Follow-up clinical evaluation will be performed 1 and 2 months after the procedure. A second esophageal HRM will be realized 3 months after the procedure, followed by endoscopic BTX injection in case of non-response and two monthly visits.
Follow-up visits will be done 6 and 12 months after the first procedure. An additional HRM will be performed at 12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Botulinum toxin injection | Experimental | Drug: Esophageal endoscopic injection of botulinum toxinEsophageal endoscopic injection of botulinum toxin |
| No injection | Sham comparator | Other: No injection of botulinum toxinNo injection of botulinum toxin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patient with non-cardiac chest pain and/or dysphagia with global Eckardt score strictly above 3 points or equal to 3 only for " chest pain " or " dysphagia " - Hypercontractile esophagus with normal esogastric junction relaxation based on the Chicago classification in high resolution manometry
- Man or woman 18-year old or older
- Normal upper gastrointestinal endoscopy within one year before inclusion
- Barium swallow without argument for external compression
- Effective form of birth control (if applicable)
Key exclusion criteria (17 listed)
- Man or woman under 18-year old
- Past history of eso-gastric surgery
- Evolutive cancer or coagulation disorders
- Absence of effective form of birth control (if applicable)
- Pregnant woman or woman who plans to become pregnant during the expected length of the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Esophageal endoscopic injection of botulinum toxinEndoscopic injection of botulinum toxin in the esophageal muscle : one hundred units of type A botulinum toxin (Botox®, Allergan) diluted in 10 mL of normal saline and injected at the lower third of the esophageal wall in 10 sites between 2 and 10 cm above the Z-line. | Drug | Botulinum toxin injection |
| No injection of botulinum toxinUpper gastro-intestinal endoscopy without any injection | Other | No injection |
Primary outcome
Clinical response
Time frame: 3 months after Botulinum toxin injection or sham procedure
Determination of the percentage of patients with clinical response defined by a global Eckardt score <3 and individual subscores <2
7 secondary outcomes
Clinical symptoms improvement
Time frame: 12 months after Botulinum toxin injection or sham procedure
Clinical symptoms improvement
Time frame: After 2 procedures of Botulinum toxin injection or sham procedure
Safety
Time frame: Days 1- 7 after procedure. Month 1,3, 4, 6 and 12 after procedure
Quality of life improvement
Time frame: At the first visit, 3 months, 6 months and 12 months after the first therapeutic procedure (botulinum toxin injection or sham procedure)
Weight gain
Time frame: 3 months, 6 months and 12 months after the first therapeutic procedure (botulinum toxin injection or sham procedure)
Modification of HRM pattern
Time frame: 3 and 12 months after the first procedure (botulinum toxin injection or sham procedure)
Clinical and paraclinical characteristics of responders versus non-responders
Time frame: 12 months after the first therapeutic procedure (botulinum toxin injection or sham procedure)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2025.
- Results publication: PubMed 30974039Mion F, Marjoux S, Subtil F, Pioche M, Rivory J, Roman S, Zerbib F. Botulinum toxin for the treatment of hypercontractile esophagus: Results of a double-blind randomized sham-controlled study. Neurogastroenterol Motil. 2019 May;31(5):e13587. doi: 10.1111/nmo.13587. Epub 2019 Apr 11.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
François MION, MD principal investigator
Hospices Civils de Lyon
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Esophageal endoscopic injection of botulinum toxin and No injection of botulinum toxin in people with Nutcracker Oesophagus, run by Hospices Civils de Lyon at 2 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical response (time frame: 3 months after Botulinum toxin injection or sham procedure). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01955174, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2025; AzTrials last refreshed its copy on 29 Oct 2026.