Efficacy of Intramuscular Steroid Injection for Chronic Cough.

Prospective Placebo-Controlled Trial of Intramuscular Steroid Administration for the Treatment of Unexplained Chronic Cough

The primary goal of this study is to test the hypothesis that injecting steroid intramuscularly is an effective treatment for unexplained chronic cough. This will be achieved through the design of a prospective, placebo-controlled, single-blind, randomized clinical trial in which one group of patients will undergo a steroid injection into the deltoid muscle and the second group will undergo a placebo injection into the deltoid muscle. Data to determine if a clinically significant difference exists between the outcomes of the two groups will be measured by a dichotomous yes/no response to improvement, the Leicester Cough Questionnaire, and a visual analogue scale for symptom severity. This will provide the answer to the general question of whether or not the intramuscular injections are clinically effective for patients with unexplained chronic cough. Furthermore, any adverse reactions will be thoroughly documented. If this hypothesized treatment is proven effective, this can greatly improve the care of chronic cough patients by allowing for an evidence-based treatment option and a treatment option that may improve access to care. While the superior laryngeal nerve (SLN) injection is typically performed by fellowship trained laryngologists, intramuscular injections could be more widely utilized by general otolaryngologists or providers in other fields of medicine.

Study Overview

• Status: Recruiting
• Conditions: Coughing; Laryngeal Disease; Chronic Cough (CC)
• Intervention / Treatment: Drug: Saline injection; Drug: Triamcinolone Acetonide Injectable Suspension

Detailed Description

A significant subset of patients are found to have "unexplained chronic cough", which is a diagnosis of exclusion. For these patients, the etiology of the cough is often not isolated. However, the cause is thought to be related to hypersensitivity and inflammation of both the nerves involved in cough sensation and/or mucosa of the larynx. A similar theory described by Driessen et al. hypothesizes that neuroinflammation related to glial cells in central and peripheral neural pathways may contribute to chronic cough in a similar way to how chronic pain is mediated by this pathway. Glial cells in the central and peripheral nervous system may be an important target for steroid hormones and their metabolites, which may have impact on inflammation and excitatory action.

Superior laryngeal nerve injections have been well studied in literature and were recently studied here at the Medical University of South Carolina in a prospective placebo-controlled trial for use in neurogenic cough. This study showed that there was a significant improvement in cough compared to placebo. This study was completed using randomization of 17 patients into the control and steroid/lidocaine injection groups. In the treatment group, 80% of patients reported improvement in symptoms, while in the control group only 14% of patients reported improvement. The Leicester Cough Questionnaire (LCQ) and visual analog scoring were used to compare cough data from pre and post injection.

The hypothesis revolves around the idea that SLN blocks may actually work systemically, so the site of injection may not be the key in cough improvement. This combined with the theory on glial cell involvement and systemic steroid use to inhibit the neuroinflammatory pathway leads us to believe that intramuscular steroid injections could improve chronic cough. Therefore, this study focuses on the use of systemic intramuscular steroids in patients with chronic cough and we hypothesize that patients will have improvement in cough severity. By opening another treatment option that could be utilized by general (non-fellowship trained) otolaryngologists, access to care and treatment may be improved for patients with chronic cough.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Kirsten Meenan; Phone Number: 843-792-6755; Email: meenan@musc.edu
• Study Contact Backup: Name: Lauren Howser; Phone Number: 843-792-6755; Email: howser@musc.edu

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29403
      • Recruiting
      • Medical University of South Carolina
      • Contact: Laryngology Office; Phone Number: 843-792-6755; Email: howser@musc.edu
      • Principal Investigator: Lauren Howser, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• History consistent with chronic unexplained or refractory cough
• Age ≥ 18

Exclusion Criteria:

• Current smokers
• Uncontrolled diabetes (A1c>7%)
• Patients on ACE inhibitors or Angiotensin II receptor blockers (ARBs)
• Abnormal pulmonary function testing (PFTs) since start of the cough
• Patients with uncontrolled obstructive sleep apnea
• Abnormal chest X-ray within past 6 months
• Uncontrolled reflux
• Prior superior laryngeal nerve injection
• Current neuromodulating medication use for chronic cough*

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo injection into deltoid (arm)	Drug: Saline injection; Saline injection into deltoid muscle (arm)
Experimental: Steroid; Triamcinolone injection into deltoid (arm)	Drug: Triamcinolone Acetonide Injectable Suspension; Triamcinolone injection into deltoid muscle (arm)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Leicester Cough Questionnaire	The primary outcome for which this study is powered is the change in mean Leicester Cough Questionnaire (LCQ) scores, both global and specific domains (physical, psychological, and social) from baseline to 1-4 weeks post-treatment. This score will be 19-133, with higher score indicating better outcomes.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dichotomous yes/no to symptom improvement	Yes/No response to cough improvement	4 weeks
Visual Analog Scale	Visual analog scale for symptom severity. This will be reported as a percentage (ratio of X marked spot to total line).	4 weeks

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Investigators: Principal Investigator: Lauren Howser, Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: October 8, 2024
• First Submitted That Met QC Criteria: October 8, 2024
• First Posted (Actual): October 10, 2024

Study Record Updates

• Last Update Posted (Actual): July 14, 2025
• Last Update Submitted That Met QC Criteria: July 9, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Chronic cough; Throat; Neurogenic cough; Unexplained cough
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Otorhinolaryngologic Diseases; Signs and Symptoms, Respiratory; Chronic Cough; Cough; Laryngeal Diseases; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Enzyme Inhibitors; Triamcinolone; Triamcinolone Acetonide; Triamcinolone hexacetonide; Triamcinolone diacetate
• Other Study ID Numbers: Pro00140403

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD can be made available at the end of the trial with de-identified patient data. A data dictionary will be provided so that the data can be fully interpreted.
• IPD Sharing Time Frame: After trial completion for 1 year
• IPD Sharing Access Criteria: Qualified researchers from academic institutions will be able to request access by contacting the PI.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes