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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01373528
Recruitment Status : Terminated
First Posted : June 15, 2011
Last Update Posted : May 18, 2012
Information provided by (Responsible Party):
Ottawa Hospital Research Institute

Brief Summary:
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 or disease Intervention/treatment Phase
Chronic Rhinosinusitis Drug: Budesonide irrigation Not Applicable

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Impact of Topical Sinonasal Budesonide Irrigation on Hypothalamic-Pituitary-Adrenal (HPA) Axis Function
Study Start Date : December 2010
Actual Primary Completion Date : May 2012
Actual Study Completion Date : May 2012

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
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.

Primary Outcome Measures :
  1. Serum cortisol levels before and after treatment [ Time Frame: 12 months ]
  2. ACTH stimulation test cortisol level [ Time Frame: 12 months ]
  3. Urinary Free Cortisol Levels [ Time Frame: Every 3 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01373528

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

Responsible Party: Ottawa Hospital Research Institute Identifier: NCT01373528     History of Changes
Other Study ID Numbers: 2010249-01H
First Posted: June 15, 2011    Key Record Dates
Last Update Posted: May 18, 2012
Last Verified: May 2012

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

Additional relevant MeSH terms:
Pituitary Diseases
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Endocrine System Diseases
Epinephryl borate
Anti-Inflammatory Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adrenergic beta-Agonists
Vasoconstrictor Agents