Doxycycline in Treating Patients With Chronic Rhinosinusitis With Nasal Polyps

• ClinicalTrials.gov Identifier: NCT02569437
• Recruitment Status: Terminated
• First Posted: October 6, 2015
• Results First Posted: January 9, 2018
• Last Update Posted: January 9, 2018
• Sponsor: Icahn School of Medicine at Mount Sinai
• Information provided by (Responsible Party): Benjamin D Malkin, Icahn School of Medicine at Mount Sinai

Tracking Information

• First Submitted Date: October 5, 2015
• First Posted Date: October 6, 2015
• Results First Submitted Date: October 31, 2017
• Results First Posted Date: January 9, 2018
• Last Update Posted Date: January 9, 2018
• Study Start Date: September 2014
• Actual Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 8, 2017)

Sino-nasal Outcome Test (SNOT 22) [ Time Frame: Baseline and 12 weeks ]

a validated 22 item quality of life questionnaire for patients with chronic rhinosinusitis. Range of 0 to 110, higher scores indicate worse outcome

Original Primary Outcome Measures (submitted: October 5, 2015)

Sino-nasal Outcome Test (SNOT 22) [ Time Frame: 12 weeks ]

a validated 22 item quality of life questionnaire for patients with chronic rhinosinusitis

Current Secondary Outcome Measures (submitted: December 8, 2017)

• Endoscopic Nasal Polyp Score [ Time Frame: Baseline and 12 weeks ]
  0- Absence of nasal polyps

  1. Polyps confined to the middle meatus and not beyond the inferior border of the middle turbinate
  2. Polyps reaching below the lower border of the middle turbinate
  3. Large polyps extending to the lower border of the inferior turbinate or medial to the middle turbinate
  4. Large polyps extending to the lower border of the inferior turbinate or medial to the middle turbinate Nasal polyp scores. The score is determined for each nostril, and the two scores added for a total nasal polyp score. Range of 0 to 8, graded on a size system from 0 to 4 and summed from the right and left nostrils.
• Middle Meatus Culture [ Time Frame: Baseline and 12 weeks ]
  Culture swab for the presence or absence of microbial growth
• Subjective Symptom Composite Scoring [ Time Frame: Baseline and 12 weeks ]
  A subjective symptom score will be extracted from the patient's score (on a scale of 0-5, where 0 defines no problems with the given symptom and 5 defines maximal problems ) on the SNOT-22 for each fo the following symptoms: "blockage/congestion," "runny nose," "post-nasal discharge," "facial pain/pressure," and "sense of taste/smell." Range of 0 to 25, with higher score reflecting worse symptoms.
• Visual Analog Scale [ Time Frame: Baseline and 12 weeks ]
  The visual analog scale for overall symptoms will be used to define disease severity. Range of 0 to 10. As per the European Position Paper 2012, mild, moderate, and severe disease will be defined as 0 to and including 3, > 3 to and including 7, and > 7 to and including 10, respectively.

Original Secondary Outcome Measures (submitted: October 5, 2015)

• Endoscopic Nasal Polyp Score [ Time Frame: 12 weeks ]
• Middle Meatus Culture [ Time Frame: 12 weeks ]
  Culture swab for the presence or absence of microbial growth
• Subjective Symptom Composite Scoring [ Time Frame: 12 weeks ]
  A subjective symptom score will be extracted from the patient's score (on a scale of 0-5) on the SNOT-22 for each fo the following symptoms: "blockage/congestion," "runny nose," "post-nasal discharge," "facial pain/pressure," and "sense of taste/smell."
• Visual Analog Scale [ Time Frame: 12 weeks ]
  The visual analog scale for overall symptoms will be used to define disease severity. As per the European Position Paper 2012, mild, moderate, and severe disease will be defined as 0 to and including 3, > 3 to and including 7, and > 7 to and including 10, respectively.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Doxycycline in Treating Patients With Chronic Rhinosinusitis With Nasal Polyps
• Official Title: The Role of Doxycycline in Management of Moderate to Severe Chronic Rhinosinusitis With Nasal Polyps
• Brief Summary: The Department of Otolaryngology at Mount Sinai is looking for adults with sinus disease with polyps, otherwise called chronic rhinosinusitis with nasal polyps (CRSwNP). Patients may be eligible to enroll in a study offering a cutting-edge therapy to help reduce symptoms and avoid surgery. The treatment combines an antibiotic (doxycycline) with oral steroids. Oral steroids are the mainstay of medical management for patients with CRSwNP. However, recent studies have shown that doxycycline helps improve symptoms as well by reducing inflammation and killing common bacteria that can cause symptoms. This study is the first to evaluate this combination regimen.
• Detailed Description: An eligible patient may be treated with either doxycycline and oral steroids OR placebo (sugar pill) and oral steroids for three weeks. Volunteers will participate in the study for to 12 weeks, and will have 4 research visits of 1 hour duration. At each study visit, the patient will under go an endoscopic evaluation and asked to complete a questionnaire describing symptoms. There is no additional cost to be enrolled in the study.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Polyp of Nasal Sinus

Intervention

• Drug: Doxycycline
  Doxycycline (200 mg PO X 1 dose on Day 1, then 100 mg PO daily) for Day 2-20
• Drug: methylprednisolone
  oral methylprednisolone: 32 mg x 5 days, 16 mg x 5 days, 8 mg x 10 days
• Drug: nasal saline spray
  nasal saline sprays: 2 sprays each nostril three times a day
• Drug: Flonase
  daily nasal steroid sprays (Flonase, 2 sprays each nostril daily).
  Other Name: nasal steroid spray
• Drug: sugar pill
  placebo pill to match doxycycline
  Other Name: placebo

Study Arms

• Experimental: Doxycycline
  Doxycycline plus oral methylprednisolone and nasal saline sprays
  Interventions:

  • Drug: Doxycycline
  • Drug: methylprednisolone
  • Drug: nasal saline spray
  • Drug: Flonase
• Placebo Comparator: Sugar pill
  placebo pill plus oral methylprednisolone for three weeks. After this, maintenance therapy which includes nasal saline sprays and daily nasal steroid sprays.
  Interventions:

  • Drug: methylprednisolone
  • Drug: Flonase
  • Drug: sugar pill

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: December 8, 2017): 49
• Original Estimated Enrollment (submitted: October 5, 2015): 90
• Actual Study Completion Date: August 2016
• Actual Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Nasal polyps on nasal endoscopy.
• The patient has moderate to severe disease, defined by moderate to severe subjective symptoms (a score greater than 3 on a 10-cm VAS).
• The patient is at least 18 years old.
• The patient is able to understand and give informed consent.

• The patient has clinically diagnosed chronic rhinosinusitis with nasal polyps according to the AAO-HNS diagnostic criteria: At least 2 of the following symptoms/signs:

  • Mucopurulent drainage (anterior, posterior, or both)
  • Nasal obstruction (congestion)
  • Facial pain-pressure-fullness
  • Decreased sense of smell
  • and symptoms lasting 12 weeks or longer.

Exclusion Criteria:

• The patient has a history of treatment with oral corticosteroids in the past 4 weeks. ,
• The patient has cystic fibrosis.
• The patient has primary ciliary dyskinesia.
• The patient has diabetes.
• The patient has had sinus surgery in the past 3 months.
• The patient has an allergy to doxycycline or related tetracyclines or glucocorticoids.
• The patient is a minor.
• The patient is a prisoner.
• The patient has a psychiatric illness or developmental delay, which would interfere with understanding of the study and provision of informed consent.
• The patient is a breastfeeding mother. The effects of the drugs used in this study (doxycycline) on breast milk are unknown and thus, these patients will be excluded from the study
• The patient has a history of HIV or other known cause of immunosuppression, or is actively taking immunosuppressive medications due to organ transplantation, rheumatoid disease, or other medical conditions.
• The patient is on penicillin; antacids containing aluminum, calcium, magnesium, or iron; bismuth subsalicylate; barbiturates; carbamazepine; and phenytoin; as well as tetracycline and Penthane.
• Pregnancy. Doxycycline, a tetracycline, is a known teratogen. For this reason women of child-bearing potential are suggested to take a form of contraception for the duration that they are taking doxycycline., Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

Pregnancy Testing. Women of childbearing potential are required to have a negative serum pregnancy test (with a sensitivity of at least 25 mIU/mL) prior to the first dose of drug. No further pregnancy tests are required since after this visit the patient will no longer be taking tetracycline after 3 weeks.

Women of childbearing potential are defined as follows:

• Patients with regular menses
• Patients with amenorrhea, irregular cycles, or using a contraceptive method that precludes withdrawal bleeding
• Women who have had a tubal ligation

Women are considered not to be of childbearing potential for the following reasons:

• The patient has undergone hysterectomy and/or bilateral oophorectomy.
• The patient is post-menopausal defined by amenorrhea for at least 1 year in a woman > 45 years old.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02569437
• Other Study ID Numbers: GCO 14-0462
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: Benjamin D Malkin, Icahn School of Medicine at Mount Sinai
• Study Sponsor: Icahn School of Medicine at Mount Sinai
• Collaborators: Not Provided

Investigators

• Principal Investigator: Benjamin D Malkin, MD; Icahns School of Medicine at Mount Sinai
• Study Chair: Satish Govindaraj, MD; Icahn School of Medicine at Mount Sinai

• PRS Account: Icahn School of Medicine at Mount Sinai
• Verification Date: December 2017