A Phase 4 interventional study of Gabapentin and Benzonatate 200 mg in Interstitial Lung Disease, sponsored by Post Graduate Institute of Medical Education and Research, Chandigarh. Not yet recruiting at 1 site in India. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-06.
Sponsored by Post Graduate Institute of Medical Education and Research, Chandigarh · Phase 4, Interventional, and Treatment
Absence of a clear standard of care and approved drug for chronic cough, the commonest symptom in ILD, calls for further research in this area. In this study, we aim to compare gabapentin and benzonatate treatment with the standard of care for treating chronic cough in ILD. We hypothesized that both gabapentin and benzonatate will be more effective than standard of care in treating chronic cough in ILD.
Cough in ILD Across ILD subtypes and geographic regions, dyspnoea on exertion and chronic cough are the most commonly reported symptoms. Chronic cough, defined by duration ≥ 8 weeks(3) is the most common symptom in ILD. Cough is typically dry, persistent, and often disproportionate to radiological disease extent.(22) In western studies, prevalence of among ILD subtypes was variable and the ILD subtype but is particularly prominent in IPF (83%) and HP (84%) compared to sarcoidosis where only 30-50% patients reports complaint of cough.(5, 7, 8). Dhooria et al reported 86% of ILD patients to be suffering from chronic cough which is yet another important distinction of ILD in India from western literature.(10) Impact of Cough on Quality of Life Chronic cough in ILD has a profound negative impact on health-related quality of life. Beyond physical discomfort, cough interferes with sleep, social interaction, communication, and emotional well-being. Studies using validated cough-specific instruments, such as the Leicester Cough Questionnaire, have demonstrated strong associations between cough severity and reduced quality-of-life scores. In patients with fibrotic ILD, cough-related quality-of-life impairment has also been linked to disease progression and poorer clinical outcomes, underscoring its relevance as a clinically meaningful symptom.(23, 24) Current Recommendations for Management of Cough in ILD The management of cough in ILD remains challenging, as robust, ILD-specific evidence is limited. Current recommendations emphasize a systematic approach, beginning with optimization of treatment for the underlying ILD and identification of potentially reversible contributors such as gastro-oesophageal reflux, upper airway disease, infection, or medication-related cough. Pharmacological treatment recommended are thalidomide in IPF and gabapentin in refractory cough however the these are mostly by low quality evidence and expert consensus.(11, 12) Gabapentin Gabapentin is a gabapentinoid originally developed as an antiepileptic agent and widely used for neuropathic pain. It binds to the α2δ subunit of voltage-gated calcium channels, leading to reduced excitatory neurotransmitter release and modulation of neuronal hyperexcitability.(25) Chronic cough is increasingly understood as a manifestation of cough reflex hypersensitivity. Gabapentin is thought to suppress cough by attenuating central neural sensitization within the cough reflex pathway, thereby reducing abnormal afferent signalling and cough frequency.(13, 14) Randomized controlled trials in patients with chronic refractory cough have demonstrated that gabapentin significantly improves cough-specific quality of life and reduces cough severity compared with placebo. Although these studies were not ILD-specific, the findings have informed guideline recommendations and clinical practice, leading to cautious off-label use of gabapentin in patients with ILD-associated refractory cough.(15)
Interstitial lung diseases (ILDs) are a group of heterogeneous disorders of the lung parenchyma characterized by inflammation and/or fibrosis resulting in dyspnoea and cough along with other symptoms and complications.(1) In a study from 3089 patients of ILD from PGIMER, Chandigarh, the crude prevalence of ILD in Northern Indian is 49.0-98.1, respectively per 100,000 population.(2) Chronic cough, defined by duration ≥ 8 weeks(3) in a common symptom in ILD with a prevalence varying from 30% - 80% among various types.(4-9) A study from PGIMER of 803 patients with ILD reported cough as the most common symptom with a prevalence of 86%.(10) Currently, there is no FDA approved treatment for cough in ILD although various treatment strategies have been studied of which some are recommended by scientific societies which reflects lacunae in the evidence for treatment of cough in ILD.(11, 12) It has been demonstrated that the sensitivity of the cough reflex is heightened in chronic cough.(13) This has opened a new modality of neuromodulation-based treatment for chronic cough. Gabapentin is a gamma-aminobutyric acid (GABA) analogue that binds to the α2δ subunit of voltage-gated calcium channels of neurons and was initially introduced as an anti-seizure medication.(14)A study by Ryan et al. showed significant relief in chronic cough with gabapentin, albeit this was a small study with a heterogeneous study population and not focused on ILD.(15) A recent meta-analysis has also shown benefit with gabapentin in chronic cough treatment.(16) Benzonatate, initially used for cough suppression in 1958, represents another possible treatment option. It acts by anesthetizing the vagal stretch receptors in the lungs and pleura, thereby reducing the activation of the cough reflex at its origin. However, no clinical trial has shown its effectiveness in ILD.
Absence of a clear standard of care and approved drug for chronic cough, the commonest symptom in ILD, calls for further research in this area. In this study, we aim to compare gabapentin and benzonatate treatment with the standard of care for treating chronic cough in ILD. We hypothesized that both gabapentin and benzonatate will be more effective than standard of care in treating chronic cough in ILD.
Benzonatate Benzonatate is a non-opioid antitussive structurally related to local anaesthetics. It exerts its antitussive effect primarily through peripheral mechanisms by anesthetizing stretch receptors in the respiratory tract and pleura, thereby dampening vagal afferent input to the cough center.(26) Evidence supporting the use of benzonatate in chronic cough is limited. Small experimental studies suggest that it may reduce cough reflex sensitivity, particularly in acute cough settings. However, controlled clinical data demonstrating sustained benefit in chronic or ILD-related cough are sparse, and its role is generally confined to symptomatic relief rather than disease-modifying therapy(27)
646 studies on the registry are indexed under Lung Diseases, Interstitial; 237 are open to participants now.
This study's planned enrollment of 177 is above the median of 54 across 355 interventional studies indexed under Lung Diseases, Interstitial.
Browse Lung Diseases, Interstitial studies →Post Graduate Institute of Medical Education and Research, Chandigarh is the lead sponsor of 290 studies on the registry; 42 are open to participants now.
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5. No contraindication to Gabapentin or Benzonatate Therapy
Exclusion Criteria:
Participants will be treated with gabapentin at starting dose of 100 mg per dose, thrice daily and up titrated by 100 mg per dose every 3 days till 300 mg per dose, thrice daily or maximum tolerated dose. Standard Therapy including anti-fibrotic agent/s, immunosuppression therapy and symptomatic therapy for cough as per departmental treatment protocol (as needed dextromethorphan lozenges) shall be continued.
Drug: Gabapentin · Other: Standard of care treatment for ILD
Participants will be treated with Benzonatate at starting dose of 100 mg per dose thrice daily and up titrated to 200 mg per dose thrice daily after 3 days. Standard Therapy including anti-fibrotic agent/s, immunosuppression therapy and symptomatic therapy for cough as per departmental treatment protocol (as needed dextromethorphan lozenges) shall be continued.
Drug: Benzonatate 200 mg · Other: Standard of care treatment for ILD
Standard Therapy including immunosuppressive and/or anti-fibrotic agent/s and symptomatic therapy for cough (as needed dextromethorphan lozenges)
Other: Standard of care treatment for ILD
Gabapentin at starting dose of 100 mg per dose, thrice daily and up titrated by 100 mg per dose every 3 days till 300 mg per dose, thrice daily or maximum tolerated dose
Benzonatate at starting dose of 100 mg per dose thrice daily and up titrated to 200 mg per dose thrice daily after 3 days
Standard Therapy including immunosuppressive and/or anti-fibrotic agent/s and symptomatic therapy for cough (as needed dextromethorphan lozenges)
Cough intensity in Gabapentin group
Difference in change in numerical rating scale (NRS 0-10) for cough from baseline to 8 weeks between the gabapentin and the standard of care groups.The cough numerical rating scale (NRS) is a simple, self-reported tool used to measure chronic cough severity, frequency, or the urge to cough on an 11-point scale from 0 to 10. 0: No cough (or no symptoms at all). 10: The most severe or worst possible cough imaginable. Higher scores: Indicate worse symptoms and greater severity.
Time frame: 8 weeks
Cough intensity in benzonatate arm
Difference in change in numerical rating scale (NRS 0-10) for cough from baseline to 8 weeks between the benzonatate and the standard of care groups. The cough numerical rating scale (NRS) is a simple, self-reported tool used to measure chronic cough severity, frequency, or the urge to cough on an 11-point scale from 0 to 10. 0: No cough (or no symptoms at all). 10: The most severe or worst possible cough imaginable. Higher scores: Indicate worse symptoms and greater severity.
Time frame: 8 weeks
Cough VAS in gabapentin group
Difference in the change in the visual analog scale (VAS) score for cough at 8 weeks between gabapentin and standard of care groups. The cough severity visual analog scale (VAS) is a 100-millimeter linear line that lets patients rate their cough intensity from \[0 mm ("no cough")\] to \[100 mm ("worst imaginable cough")\]. Format: A straight horizontal or vertical line measuring exactly 100 mm long. Anchors: The bottom or left end is marked 0 ("No cough"), and the top or right end is marked 100 ("Worst cough"). Scoring: The patient makes a mark on the line matching their symptom severity, and the distance in millimeters from zero to the mark is measured. Higher scores indicate worse cough.
Time frame: 8 weeks
Cough VAS in benzonatate arm
Difference in the change in the visual analog scale (VAS) score for cough at 8 weeks between benzonatate and standard of care groups. The cough severity visual analog scale (VAS) is a 100-millimeter linear line that lets patients rate their cough intensity from \[0 mm ("no cough")\] to \[100 mm ("worst imaginable cough")\]. Format: A straight horizontal or vertical line measuring exactly 100 mm long. Anchors: The bottom or left end is marked 0 ("No cough"), and the top or right end is marked 100 ("Worst cough"). Scoring: The patient makes a mark on the line matching their symptom severity, and the distance in millimeters from zero to the mark is measured. Higher scores indicate worse cough.
Time frame: 8 weeks
Leicester Cough questionnaire (LCQ) score in gabapentin arm
Difference in the change in leicester cough questionnaire (LCQ) total score at 8 weeks between gabapentin and standard of care groups.The Leicester Cough Questionnaire (LCQ) is a brief, 19-item self-administered tool used to measure the impact of a chronic cough on an adult's quality of life over the previous two weeks. The questionnaire splits the 19 items into three specific areas of health: Physical (8 items): Evaluates chest or stomach pains, phlegm, hoarseness, sleep disruption, energy levels, and coughing bouts. Psychological (7 items): Measures tiredness, feelings of control, embarrassment, anxiety, frustration, and worry about serious illness. Social (4 items): Assesses interference with jobs, daily enjoyment, conversations, and relationships. Scoring and Interpretation: Scale: Each item is rated on a 7-point Likert scale (ranging from 1 to 7). Total Score Range: From 3 to 21. Higher scores indicate a better quality of life and less impact from the cough
Time frame: 8 weeks
Leicester Cough questionnaire score in the benzonatate arm
Difference in the change in leicester cough questionnaire (LCQ) total score at 8 weeks between benzonatate and standard of care groups.The Leicester Cough Questionnaire (LCQ) is a brief, 19-item self-administered tool used to measure the impact of a chronic cough on an adult's quality of life over the previous two weeks. The questionnaire splits the 19 items into three specific areas of health: Physical (8 items): Evaluates chest or stomach pains, phlegm, hoarseness, sleep disruption, energy levels, and coughing bouts. Psychological (7 items): Measures tiredness, feelings of control, embarrassment, anxiety, frustration, and worry about serious illness. Social (4 items): Assesses interference with jobs, daily enjoyment, conversations, and relationships. Scoring and Interpretation: Scale: Each item is rated on a 7-point Likert scale (ranging from 1 to 7). Total Score Range: From 3 to 21. Higher scores indicate a better quality of life and less impact from the cough
Time frame: 8 weeks
ILD-related quality of life assess using the King's brief interstitial lung disease score in gabapantin arm
Difference in the change in king's brief interstitial lung disease quality of life groups questionnaire (K-BILD) at 8 weeks between gabapentin and standard of care. The King's Brief Interstitial Lung Disease (K-BILD) questionnaire is a validated, patient-reported outcome tool to measure the health-related quality of life (HRQoL) in adults living with interstitial lung disease (ILD). It consists of 15 items scored on a 7-point Likert scale. It assesses the patient's respiratory health and well-being over the preceding 2 weeks. Scoring: The total score and separate domain scores range from 0 to 100, where 100 represents the best possible health status and 0 represents the worst.
Time frame: 8 weeks
ILD-related quality of life assessed using the king's brief interstitial lung disease quality of life groups questionnaire (K-BILD)
Difference in the change in king's brief interstitial lung disease quality of life groups questionnaire (K-BILD) at 8 weeks between benzonatate and standard of care. The King's Brief Interstitial Lung Disease (K-BILD) questionnaire is a validated, patient-reported outcome tool to measure the health-related quality of life (HRQoL) in adults living with interstitial lung disease (ILD). It consists of 15 items scored on a 7-point Likert scale. It assesses the patient's respiratory health and well-being over the preceding 2 weeks. Scoring: The total score and separate domain scores range from 0 to 100, where 100 represents the best possible health status and 0 represents the worst.
Time frame: 8 weeks
Treatment-emergent adverse effects
difference in the incidence of treatment-emergent adverse effects between the study groups. The averse effects will include drowsiness, dizziness, throat numbness, nausea, constipation, and any other side effects reported by the study subjects
Time frame: 8 weeks
Plan to share: Yes — Deidentified data related to study's primary and secondary outcomes
Supporting information: Study protocol, Sap
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Post Graduate Institute of Medical Education and Research, Chandigarh