Laryngeal Cryotherapy for Refractory Neurogenic Cough

Upper-Airway Cough Syndrome Clinical Trial

Official title:

To Determine the Efficacy of Topical Cryotherapy on Supraglottic Laryngeal Mucosa in the Treatment of Chronic Neurogenic Cough in Adult Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05665244
• Other study ID #: Cryotherapy
• Status: Recruiting
• Start date: December 26, 2022
• Est. completion date: December 30, 2024

Study information

• Verified date: January 2024
• Source: University of Texas Southwestern Medical Center
• Contact: Shumon Dhar, MD
• Phone: 214-645-7034
• Email: Shumon.Dhar[@]UTSouthwestern.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study aims to evaluate the safety and efficacy of upper aerodigestive tract cryotherapy treatment in patients with refractory neurogenic cough in a prospective pilot study with a validated patient reported outcome measure

Description:

This study aims to test a new type of treatment for patients suffering from chronic cough, also known as upper airway cough syndrome. The new treatment involves the use of laryngeal cryotherapy which is the therapeutic freezing of tissue in the throat to numb the overactive sensory nerves in the throat which is believed to reduce cough symptoms. Patients will first undergo a flexible scope of the throat (laryngoscopy) to test for hypersensitive areas in the throat, then undergo the cryotherapy procedure in the office. After that, patients will be followed up in the clinic with the usual standard of care visits and undergo validated cough surveys to track their cough symptoms after the procedure. Possible side effects to this procedure are listed in detail below, and include temporary throat pain and coughing.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 25
• Est. completion date: December 30, 2024
• Est. primary completion date: December 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult patients 18 years or older with diagnosis of neurogenic cough

• Neurogenic cough is a diagnosis of exclusion applied to persistent cough (8 weeks or longer)

• Negative workup for other causes, including sinonasal allergies/chronic sinusitis, cough-variant asthma, and GERD

• Patient willing to participate in a clinical trial

Exclusion Criteria:

• Uncontrolled reflux (scoring on Reflux Symptom index of 13 or higher)

• Vocal fold abnormalities or impairment

• History of asthma or other underlying lung condition not adequately treated or controlled

• Uncontrolled Allergic Rhinitis (Total Nasal Symptom Score >6, which would indicate moderate disease32)

• Reported symptom of postnasal drip

• Current smoker

• Current neuromodulator medication use

• Patient unwilling to participate in clinical trial or sign an informed consent

• End stage medical disease with poor life expectancy

• Medical instability deemed by the investigators as a contraindication for enrollment

• Abnormal Chest X-ray

• Abnormal pulmonary function testing (PFTs)

• Positive local allergy panel (combined RAST testing)

Related Conditions & MeSH terms

• Cough
• Upper-Airway Cough Syndrome

Intervention

Procedure:
• Laryngeal cryotherapy
Laryngeal cryotherapy is the therapeutic freezing of tissue in the throat to numb the overactive sensory nerves in the throat. This technique is believed to reduce cough symptoms in this study.

Device:
• Cryoprobe
Cryoprobe is FDA approved for use for the destruction of unwanted tissue along the respiratory tract

Locations

Country	Name	City	State
United States	UT Southwestern Medical Center	Dallas	Texas

Sponsors (1)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (11)

Aviv JE, Martin JH, Kim T, Sacco RL, Thomson JE, Diamond B, Close LG. Laryngopharyngeal sensory discrimination testing and the laryngeal adductor reflex. Ann Otol Rhinol Laryngol. 1999 Aug;108(8):725-30. doi: 10.1177/000348949910800802. — View Citation

DiBardino DM, Lanfranco AR, Haas AR. Bronchoscopic Cryotherapy. Clinical Applications of the Cryoprobe, Cryospray, and Cryoadhesion. Ann Am Thorac Soc. 2016 Aug;13(8):1405-15. doi: 10.1513/AnnalsATS.201601-062FR. — View Citation

Farooqi MAM, Cheng V, Wahab M, Shahid I, O'Byrne PM, Satia I. Investigations and management of chronic cough: a 2020 update from the European Respiratory Society Chronic Cough Task Force. Pol Arch Intern Med. 2020 Sep 30;130(9):789-795. doi: 10.20452/pamw.15484. Epub 2020 Jul 6. Erratum In: Pol Arch Intern Med. 2021 Feb 26;131(2):220. — View Citation

Foote AG, Thibeault SL. Sensory Innervation of the Larynx and the Search for Mucosal Mechanoreceptors. J Speech Lang Hear Res. 2021 Feb 17;64(2):371-391. doi: 10.1044/2020_JSLHR-20-00350. Epub 2021 Jan 19. — View Citation

Gibson P, Wang G, McGarvey L, Vertigan AE, Altman KW, Birring SS; CHEST Expert Cough Panel. Treatment of Unexplained Chronic Cough: CHEST Guideline and Expert Panel Report. Chest. 2016 Jan;149(1):27-44. doi: 10.1378/chest.15-1496. Epub 2016 Jan 6. — View Citation

Shembel AC, Rosen CA, Zullo TG, Gartner-Schmidt JL. Development and validation of the cough severity index: a severity index for chronic cough related to the upper airway. Laryngoscope. 2013 Aug;123(8):1931-6. doi: 10.1002/lary.23916. Epub 2013 Jun 4. — View Citation

Simpson CB, Amin MR. Chronic cough: state-of-the-art review. Otolaryngol Head Neck Surg. 2006 Apr;134(4):693-700. doi: 10.1016/j.otohns.2005.11.014. — View Citation

Simpson CB, Tibbetts KM, Loochtan MJ, Dominguez LM. Treatment of chronic neurogenic cough with in-office superior laryngeal nerve block. Laryngoscope. 2018 Aug;128(8):1898-1903. doi: 10.1002/lary.27201. Epub 2018 Apr 18. — View Citation

Strohl MP, Chang JL, Dwyer CD, Young VN, Rosen CA, Cheung SW. Laryngeal Adductor Reflex Movement Latency Following Tactile Stimulation. Otolaryngol Head Neck Surg. 2022 Apr;166(4):720-726. doi: 10.1177/01945998211025517. Epub 2021 Jul 13. — View Citation

Strohl MP, David AP, Dwyer CD, Rosen CA, Young VN, Chang JL, Cheung SW. Aesthesiometer-Based Testing for Laryngopharyngeal Hyposensitivity. Laryngoscope. 2022 Jan;132(1):163-168. doi: 10.1002/lary.29761. Epub 2021 Jul 20. — View Citation

Strohl MP, Young VN, Dwyer CD, Bhutada A, Crawford E, Chang JL, Rosen CA, Cheung SW. Novel Adaptation of a Validated Tactile Aesthesiometer to Evaluate Laryngopharyngeal Sensation. Laryngoscope. 2021 Jun;131(6):1324-1331. doi: 10.1002/lary.28947. Epub 2020 Jul 31. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improved quality of life of patients suffering from chronic cough	This is a validated patient reported outcome measure for chronic cough. This is a questionnaire of 10 questions about cough symptoms, each question is rated on a scale of 0-4 by the patient. The higher the CSI total score the worsen the cough symptoms are for the patient. The CSI will be compared across 5 time points (Pre-Laryngeal Cryotherapy, 1 week post cryotherapy, 1 month post cryotherapy, 3 months post cryotherapy and 6 months post cryotherapy) using repeated measures one-way ANOVA. Post-hoc pair-wise comparisons with Bonferroni correction will be used, as appropriate.	2 years
Primary	Pre and Post-time point differences.	Sample size of 25 was determined based on expectations of a detectable significant within-group using a repeated measures ANOVA across 5 time points (add in the time points) with an alpha level of 0.0125, 85% power, and 1.246 effect size (based on previous work by Simpson et al PMID: 29668037.) needed to observe pre-post time point differences.	2 years
Secondary	Pre- and post-treatment measures for the cryotherapy treatment group	This measure is the pre cryotherapy and 1 week post cryotherapy laryngeal aesthesiometer testing. This is a type of validated sensory testing of the larynx performed during an office flexible laryngoscopy where calibrated monofilaments are used to assess how sensitive certain parts of the larynx are. The data collected will be if a specific monofilament (size 6-0, 5-0, and 4-0) can trigger or not trigger a cough reflex when applied to specific subsites of the larynx (aryepiglottic fold, laryngeal aspect of epiglottis, false vocal fold, arytenoid prominence, and lateral and medial piriform sinus	2 years