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

June 12, 2011
May 16, 2012
December 2010
May 2012   (final data collection date for primary outcome measure)
  • 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 ]
Same as current
Complete list of historical versions of study NCT01373528 on ClinicalTrials.gov Archive Site
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Impact of Topical Sinonasal Budesonide Irrigation on Hypothalamic-Pituitary-Adrenal Axis Function
Impact of Topical Sinonasal Budesonide Irrigation on Hypothalamic-Pituitary-Adrenal (HPA) Axis Function

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.

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.

Interventional
Not Provided
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Chronic Rhinosinusitis
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.
Experimental: Budesonide
Intervention: Drug: Budesonide irrigation
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
2
May 2012
May 2012   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Canada
 
NCT01373528
2010249-01H
Yes
Ottawa Hospital Research Institute
Ottawa Hospital Research Institute
Not Provided
Principal Investigator: Kilty Shaun, MD OHRI
Ottawa Hospital Research Institute
May 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP