Impact of Topical Sinonasal Budesonide Irrigation on Hypothalamic-Pituitary-Adrenal Axis Function

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier:
NCT01373528
First received: June 12, 2011
Last updated: May 16, 2012
Last verified: May 2012
  Purpose

Chronic rhinosinusitis (CRS) is a complex inflammatory disease that is treated primarily with sinus surgery and the long-term use of topical steroid therapy. Budesonide irrigation is a common method of topical steroid treatment for these patients. However, the effects of budesonide irrigation on the hypothalamic-pituitary-adrenal (HPA) axis in patients with CRS following sinus surgery, is as of yet not defined. The objective of this study is to determine if topical sinonasal budesonide steroid irrigation leads to acute recoverable and/or long-term suppression of the HPA axis. Participants in this prospective cohort study will have CRS and have recently undergone endoscopic sinus surgery. They will also have had planned use of budesonide irrigations as their postoperative medical treatment. The acute effects of this treatment on the HPA axis will be evaluated using serial serum cortisol measurements both the day before and the day of the first budesonide irrigation. The long-term effect of sinonasal budesonide irrigation will be evaluated using both a pre- and post-treatment adrenocorticotropic hormone (ACTH) stimulation test as well as repeated urine free cortisol levels over the length of the study. The results will determine the need for additional steroids when patients stop treatment or with a physiologic stressful event.


Condition Intervention
Chronic Rhinosinusitis
Drug: Budesonide irrigation

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Impact of Topical Sinonasal Budesonide Irrigation on Hypothalamic-Pituitary-Adrenal (HPA) Axis Function

Resource links provided by NLM:


Further study details as provided by Ottawa Hospital Research Institute:

Primary Outcome Measures:
  • Serum cortisol levels before and after treatment [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • ACTH stimulation test cortisol level [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Urinary Free Cortisol Levels [ Time Frame: Every 3 months ] [ Designated as safety issue: Yes ]

Enrollment: 2
Study Start Date: December 2010
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Budesonide Drug: Budesonide irrigation
A budesonide (1 mg) in saline (240 mL) irrigation solution is applied to the sinonasal cavities twice daily. 120 mL of the solution is applied via irrigation in the AM, and 120 mL again in the PM.

Detailed Description:

CRS is an inflammatory disease of the paranasal sinuses that is difficult to treat. Current treatment strategies rely upon medical treatment with the long-term daily use of a topical corticosteroid as its foundation. Once medical therapy becomes ineffective at controlling CRS and its resultant symptoms, surgical treatment is offered. Following surgery, patients must again continue with medical treatment to control the inflammation present in CRS. Previously, topical steroids could be applied using only a commercially prepared applicator that is effective at treating no more than the front of the nose and parts of the paranasal sinuses. However, relatively new nasal saline irrigation devices have made it possible to treat all of the paranasal sinuses. Corticosteroid medication can be added directly to the saline irrigation. In an operated patient the sinus openings have been greatly enlarged which then allows the irrigation to more effectively reach all of the paranasal sinuses. Therefore, irrigation with a corticosteroid solution allows for better delivery of the corticosteroid medication to treat the mucosal inflammation that is widely present. More effective treatment of the paranasal sinus inflammation thereby leads to improved control of inflammation and to the alleviation of patient symptoms such as chronic facial and dental pain, headache, obstructed nasal breathing, loss of smell and discharge from the nose. As of yet, with this method of treatment it has not been determined whether there is significant systemic absorption and a resultant suppression of the HPA axis.

The investigators hypothesize that:

  1. a single 0.5 mg dose of budesonide will result in acute but recoverable suppression of pituitary adrenocorticotrophic hormone (ACTH) secretion with a resultant transient decrease in adrenal cortisol production; and that
  2. the long term use of budesonide, 0.5 mg twice daily (BID), will result in a gradual and cumulative suppression of the HPA axis to the extent that significant hypocortisolism will be present when budesonide irrigation is discontinued necessitating replacement glucocorticoid therapy.

Specific Aim of Project This study will determine if there is acute recoverable and long-term suppression of the HPA axis when budesonide irrigations are used in patients with CRS following endoscopic sinus surgery. This important information is currently not available in the literature.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Consenting adult patients (age ≥18) who are diagnosed with CRS
  • Patient already determined to need surgical treatment having failed medical management
  • Patients planned to be treated with budesonide irrigations as postoperative maintenance therapy

Exclusion Criteria:

  • Patients with pre-operative symptoms and signs of HPA dysfunction
  • Patients with signs and symptoms of untreated endocrine disorders such as hypothyroidism, hypopituitarism, hypogonadism. Screening for thyroid disease will be done with a TSH, T3 and free T4 for each participant.
  • Patients with known history of liver disease or abnormal AST/ALT lab tests
  • Any history of oral glucocorticoid use in the past 4 months
  • Patients with a known history of glaucoma
  • Patients with known tuberculosis (TB)- active or latent
  • Patients taking drugs that affect cortisol synthesis (mifepristomine, itraconazole, ketoconazole, erythromycin, clarithromycin, cimetidine) or protein binding drugs (estrogens and androgens)
  • A known sensitivity to topical budesonide
  • Pregnant and/or breast feeding woman
  • Presence of multiple co-morbidities such as poorly controlled diabetes, chronic renal failure, hepatic failure
  • Inability to provide informed consent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01373528

Locations
Canada, Ontario
Ottawa Hospital Riverside Campus
Ottawa, Ontario, Canada, K1H 4E9
Sponsors and Collaborators
Ottawa Hospital Research Institute
Investigators
Principal Investigator: Kilty Shaun, MD OHRI
  More Information

No publications provided

Responsible Party: Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier: NCT01373528     History of Changes
Other Study ID Numbers: 2010249-01H
Study First Received: June 12, 2011
Last Updated: May 16, 2012
Health Authority: Canada: Health Canada

Keywords provided by Ottawa Hospital Research Institute:
Sinonasal Budesonide
Endoscopic sinus surgery
Hypothalamic-Pituitary-Adrenal Axis Function

Additional relevant MeSH terms:
Budesonide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on July 24, 2014