Full published results of this study can be found at this link.  The full manuscript can be downloaded free of charge.

Study Start Date: 07/01/2015
Study End Date: 07/31/2020

Prospective randomized clinical trial of doxepin in canine laryngeal paralysis.

Ageing Labrador Retrievers are often affected by a disorder causing paralysis of the vocal chords known as laryngeal paresis/paralysis (LP). This interferes with breathing, clearance of debris from the airways, swallowing, and can result in heat stroke, pneumonia and death. Diagnosis is based on examining the movement of the vocal chords under anesthesia, and by ultrasound examination of the vocal chords. Treatment is surgical, which relieves the obstruction of the airways, but predisposes the dog to pneumonia, and is expensive. Therefore, medical treatment that improved vocal chord function could provide a cheaper and safer alternative.

Clinicians have observed improvement of LP after administering a drug called doxepin. However, no controlled studies have examined whether this effect is real, how frequently patients improve, how much they improve, and for how long the improvement is sustained.

We will examine the effect of doxepin administered for one month to Labrador Retrievers with non-critical LP and comparing it to a similarly administered placebo. We will assess the client’s impression of improvement using a standardized questionnaire as well as changes in vocal chord movement to determine whether this drug is effective in treating LP.

Study Design:
Prospective randomized, placebo-controlled 1-month clinical trial.

Sample Size:
40 Labrador Retrievers with confirmed LP (20 placebo, 20 treatment)

Inclusion Criteria:

• Labrador Retriever
• Recent, untreated diagnosis of LP OR clinical suspicion of LP (diagnosis will be confirmed prior to enrollment)
• Non-critical LP (not requiring immediate surgery)
• No serious co-morbidities
• Clients able to present their pets to Red Bank Veterinary Hospital in Tinton Falls, NJ for the initial and follow-up visits.

Exclusion Criteria:

• Dogs other than Labrador Retrievers.
• Clients unable to present their pets to Red Bank Veterinary Hospital in Tinton Falls, NJ, for initial and follow-up evaluations.
• Unstable LP, as assessed by client and clinician, such that the patient requires immediate surgical intervention or is likely to require intervention within the study period.
• Serious co-morbidities identified through the routine evaluation of the patient (e.g. hypothyroidism, severe blood dyscrasias, neoplasia detected with physical examination, routine bloodwork or thoracic radiographs) that might affect laryngeal function or preclude completion of the study.
• History of conditions with contraindications to doxepin therapy (urine retention, glaucoma, severe cardiac disease).
• Administration of drugs known to increase doxepin concentrations, or potentiate serotonin syndrome. These include: monamine oxidase inhibitors, cimetidine, meperidine, dextromethorphan, quinidine, serum serotonin reuptake inhibitors, and anticholinergic agents.

Study Controls:
Enrolled patients will be randomized to either placebo or doxepin, using a 1:1 allocation.

Study Endpoints:
The patients will be treated for 1 month. Client questionnaires evaluating responses and quality of life prior to and after 1 month will be compared for both groups. Clients in the placebo arm at the end of 1 month will be given the option of open-label treatment with doxepin for an additional month. All clients wishing to continue administering doxepin beyond the study endpoint will do so at their own expense.

Samples:
All potential patients will undergo routine bloodwork and thyroid testing prior to enrollment.

Costs/Reimbursements

• Clients will be responsible for the initial evaluation and diagnosis of LP. An estimate of these costs, including clinical evaluation, anesthesia and laryngeal examination can be provided by the study coordinator, Angela Lanoce.
• Costs of bloodwork prior to enrollment will be covered by the investigators.
• Enrolled dogs will undergo laryngeal ultrasound prior to commencing the study and after one month. The costs of ultrasound will be covered by the investigators.
• All clients whose pets complete the study will be given $100.
• Costs of emergency surgery during or after the study will be the client’s responsibility.

Full Disclosure information:
The study is funded by a grant from the ACVIM Foundation.
The investigator does not have a conflict of interest.
The study will be published if results are negative
The study will be reported on VIN
The authors will acknowledge VIN if the study is published