Onabotulinum Toxin A (Botox) in the Treatment of Transfer Dysphagia

NCT04695600 | Unknown Phase 2 FDA Drug

• 1 other identifier: IEC-1175/04.12.2020
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Dysphagia in patients with stroke, multiple sclerosis, parkinsonism or dystonia can occur due to relative hypertonia of the cricopharyngeus muscle. In the resting state, muscle is contracted and relaxes only during deglutition. Treatment of dysphagia by injecting botulinum toxin in the cricopharyngeus was described by Schneider et al. in 1994. More than 100 cases have been described after that, however there are no randomized controlled trials. A meta-analysis from Cochrane has also concluded that there is no sufficient evidence to conclude regarding the efficacy and safety of Botulinum toxin injection in cricopharyngeal dysfunction. So this study is necessary to fill this void in knowledge

Conditions

Transfer Dysphagia; Oropharyngeal Dysphagia; Cricopharyngeus Muscle Dysfunction; Dysphagia, Late Effect of Stroke

Keywords

Botulinum toxin; Cricopharyngeal dysfunction

Outcome Measures

Primary Outcomes (2)

• Proportion of patients who have moderate to significant improvement in swallowing function on self assessment and clinical swallowing assessment - 3 weeks

  To compare the proportion of patients who have moderate to significant improvement in swallowing function on self assessment and clinical swallowing assessment at 3 weeks post injection amongst those who received onabotulinum toxin (Botox, Allergan, Irvine, CA) and those who received placebo.

  3 weeks

• Proportion of patients who have moderate to significant improvement in swallowing function on self assessment and clinical swallowing assessment - 3 months

  To compare the proportion of patients who have moderate to significant improvement in swallowing function on self assessment and clinical swallowing assessment at 3 months post injection amongst those who received onabotulinum toxin (Botox, Allergan, Irvine, CA) and those who received placebo.

  3 months

Secondary Outcomes (3)

• Proportion of patients with improvement in swallowing related parameters on video fluoroscopy, flexible endoscopic evaluation of swallowing and esophageal manometry - 3 weeks

  3 weeks

• Proportion of patients with improvement in swallowing related parameters on video fluoroscopy, flexible endoscopic evaluation of swallowing and esophageal manometry - 3 months

  3 months

• Adverse effects

  3 months

Study Arms (2)

Botulinum toxin arm

EXPERIMENTAL

100 units of botulinum toxin (Botox, Allergan, CA) diluted in 2.5 mL of normal saline will be injected into the cricopharyngeus muscle under direct endoscopic vision using an esophago-gastro-duodenoscope (GIF 190,Olympus). The procedure will be done under general anesthesia in the endoscopy suite as the position of the endoscope is unstable at cricopharynx and the muscle needs to be relaxed during the procedure. Pre-procedure a Ryle's tube will be placed into the stomach under endoscopic guidance which will be kept a day post procedure. Cricopharyngeus muscle will be identified as the muscle at the upper esophageal sphincter located just behind the laryngeal opening. Botulinum toxin will be injected into the muscle in four aliquots into each quadrant using 23 G needle (160cm). Post procedure patient will be observed for an hour for any untoward adverse event

Drug: Botulinum Toxin Type A Injection [Botox]

Placebo arm

PLACEBO COMPARATOR

2.5 mL of Normal saline will be injected into the cricopharyngeus muscle under direct endoscopic vision using an esophago-gastro-duodenoscope (GIF 190,Olympus). The procedure will be done under general anesthesia in the endoscopy suite as the position of the endoscope is unstable at cricopharynx and the muscle needs to be relaxed during the procedure. Pre-procedure a Ryle's tube will be placed into the stomach under endoscopic guidance which will be kept a day post procedure. Cricopharyngeus muscle will be identified as the muscle at the upper esophageal sphincter located just behind the laryngeal opening. Post procedure patient will be observed for an hour for any untoward adverse event

Drug: Botulinum Toxin Type A Injection [Botox]

Interventions

Botulinum Toxin Type A Injection [Botox] DRUG

100 units of Botulinum toxin A (Botox, Allergan, CA) under endoscopic guidance will be injected in the cricopharyngeus muscle

Botulinum toxin arm; Placebo arm

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients attending neurology OPD with swallowing dysfunction due to central nervous system dysfunction
• At least 14 years of age of all sexes
• mRS (modified Rankin scale) of ≤3 at time of study enrolment
• In case of post stroke dysphagia, at least 6 months have passed following stroke
• Willing to undergo swallowing assessment clinically and with video fluoroscopy, flexible upper GI endoscopy and esophageal manometry before and after the injection
• Above investigations show impaired cricopharyngeal relaxation, adequate pharyngeal strength and anterocephalad laryngeal movement
• Ready to provide consent for Botulinum neurotoxin injection.
• Willing to adhere to protocol and comply with follow up visits
• No major neurologic or systemic medical condition that reduces life expectancy to less than 1 year based on clinical prediction scores

You may not qualify if:

• Diagnosed cases of neuromuscular disorders of the peripheral nervous system and ALS
• mRS at time of enrolment \>3
• Patients with expected life expectancy less than 1 year due to primary disease or co morbidity based on clinical prediction scores
• Known allergy to botulinum neurotoxin or its preservatives/excipients
• Received botulinum toxin for any indication in the last 12 weeks
• Those with known antibodies against Botulinum neurotoxin A
• Those who underwent myotomy of the cricopharyngeus muscle
• Those who had undergone procedures like denervation of the cervical musculature
• Women of childbearing potential who are not using adequate contraception or who are pregnant and lactating
• Not willing to provide consent

Sponsors & Collaborators

• All India Institute of Medical Sciences: lead

Study Sites (1)

All India Institute of Medical Sciences, New Delhi

New Delhi, National Capital Territory of Delhi, 110029, India

RECRUITING

Related Publications (11)

• Terre R, Valles M, Panades A, Mearin F. Long-lasting effect of a single botulinum toxin injection in the treatment of oropharyngeal dysphagia secondary to upper esophageal sphincter dysfunction: a pilot study. Scand J Gastroenterol. 2008;43(11):1296-303. doi: 10.1080/00365520802245403.

  PMID: 18649151 BACKGROUND

• Parameswaran MS, Soliman AM. Endoscopic botulinum toxin injection for cricopharyngeal dysphagia. Ann Otol Rhinol Laryngol. 2002 Oct;111(10):871-4. doi: 10.1177/000348940211101002.

  PMID: 12389853 BACKGROUND

• Schneider I, Thumfart WF, Pototschnig C, Eckel HE. Treatment of dysfunction of the cricopharyngeal muscle with botulinum A toxin: introduction of a new, noninvasive method. Ann Otol Rhinol Laryngol. 1994 Jan;103(1):31-5. doi: 10.1177/000348949410300105.

  PMID: 8291857 BACKGROUND

• Regan J, Murphy A, Chiang M, McMahon BP, Coughlan T, Walshe M. Botulinum toxin for upper oesophageal sphincter dysfunction in neurological swallowing disorders. Cochrane Database Syst Rev. 2014 May 6;2014(5):CD009968. doi: 10.1002/14651858.CD009968.pub2.

  PMID: 24801118 BACKGROUND

• Samal P, Goyal V, Makharia GK, Das CJ, Gorthi SP, Y VV, Singh MB, Srivastava MVP. Transfer Dysphagia Due to Focal Dystonia. J Mov Disord. 2018 Sep;11(3):129-132. doi: 10.14802/jmd.17081. Epub 2018 Sep 30.

  PMID: 30304925 BACKGROUND

• Moerman MB. Cricopharyngeal Botox injection: indications and technique. Curr Opin Otolaryngol Head Neck Surg. 2006 Dec;14(6):431-6. doi: 10.1097/MOO.0b013e328010b85b.

  PMID: 17099352 BACKGROUND

• Ali GN, Wallace KL, Laundl TM, Hunt DR, deCarle DJ, Cook IJ. Predictors of outcome following cricopharyngeal disruption for pharyngeal dysphagia. Dysphagia. 1997 Summer;12(3):133-9. doi: 10.1007/PL00009527.

  PMID: 9190098 BACKGROUND

• Allen J, White CJ, Leonard R, Belafsky PC. Effect of cricopharyngeus muscle surgery on the pharynx. Laryngoscope. 2010 Aug;120(8):1498-503. doi: 10.1002/lary.21002.

  PMID: 20665853 BACKGROUND

• Kuhn MA, Belafsky PC. Management of cricopharyngeus muscle dysfunction. Otolaryngol Clin North Am. 2013 Dec;46(6):1087-99. doi: 10.1016/j.otc.2013.08.006. Epub 2013 Oct 11.

  PMID: 24262961 BACKGROUND

• Kelly EA, Koszewski IJ, Jaradeh SS, Merati AL, Blumin JH, Bock JM. Botulinum toxin injection for the treatment of upper esophageal sphincter dysfunction. Ann Otol Rhinol Laryngol. 2013 Feb;122(2):100-8. doi: 10.1177/000348941312200205.

  PMID: 23534124 BACKGROUND

• Zaninotto G, Marchese Ragona R, Briani C, Costantini M, Rizzetto C, Portale G, Zanetti L, Masiero S, Costantino M, Nicoletti L, Polidoro A, Feltrin G, Angelini C, Ancona E, Guidolin D, Parenti AR. The role of botulinum toxin injection and upper esophageal sphincter myotomy in treating oropharyngeal dysphagia. J Gastrointest Surg. 2004 Dec;8(8):997-1006. doi: 10.1016/j.gassur.2004.09.037.

  PMID: 15585387 BACKGROUND

MeSH Terms

Conditions

Deglutition Disorders

Interventions

Botulinum Toxins, Type A

Condition Hierarchy (Ancestors)

Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Pharyngeal Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors

Study Officials

• Arunmozhimaran Elavarasi, MD DM

  All India Institute of Medical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Arunmozhimaran Elavarasi, MD DM

CONTACT

+919013844274; arun_ela@yahoo.com

Pramod Garg, MD DM

CONTACT

+919810038116; pkgarg@aiims.ac.in

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: • Participant, investigator, assessor and the statistician will be blinded to the treatment allocation
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Department of Neurology

Study Record Dates

• First Submitted: January 3, 2021
• First Posted: January 5, 2021
• Study Start: August 22, 2023
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: September 13, 2023

Record last verified: 2023-09

Locations

IN (1)