Doxycycline in Treating Patients With Chronic Rhinosinusitis With Nasal Polyps

The Role of Doxycycline in Management of Moderate to Severe Chronic Rhinosinusitis With Nasal Polyps

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.

Study Overview

• Status: Terminated
• Conditions: Polyp of Nasal Sinus
• Intervention / Treatment: Drug: Doxycycline; Drug: methylprednisolone; Drug: nasal saline spray; Drug: Flonase; Drug: sugar pill

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
• Enrollment (Actual): 49
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Doxycycline; Doxycycline plus oral methylprednisolone and nasal saline sprays	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 Names: nasal steroid spray
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.	Drug: methylprednisolone; oral methylprednisolone: 32 mg x 5 days, 16 mg x 5 days, 8 mg x 10 days; Drug: Flonase; daily nasal steroid sprays (Flonase, 2 sprays each nostril daily).; Other Names: nasal steroid spray; Drug: sugar pill; placebo pill to match doxycycline; Other Names: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sino-nasal Outcome Test (SNOT 22)	a validated 22 item quality of life questionnaire for patients with chronic rhinosinusitis. Range of 0 to 110, higher scores indicate worse outcome	Baseline and 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endoscopic Nasal Polyp Score	0- Absence of nasal polyps; Polyps confined to the middle meatus and not beyond the inferior border of the middle turbinate; Polyps reaching below the lower border of the middle turbinate; Large polyps extending to the lower border of the inferior turbinate or medial to the middle turbinate; 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.	Baseline and 12 weeks
Middle Meatus Culture	Culture swab for the presence or absence of microbial growth	Baseline and 12 weeks
Subjective Symptom Composite Scoring	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.	Baseline and 12 weeks
Visual Analog Scale	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.	Baseline and 12 weeks

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• 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

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: October 5, 2015
• First Submitted That Met QC Criteria: October 5, 2015
• First Posted (Estimate): October 6, 2015

Study Record Updates

• Last Update Posted (Actual): January 9, 2018
• Last Update Submitted That Met QC Criteria: December 8, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: doxycycline; oral methylprednisone; sinusitis with nasal polyps
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Pathological Conditions, Anatomical; Nose Diseases; Nasal Polyps; Polyps; Physiological Effects of Drugs; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Dermatologic Agents; Anti-Bacterial Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Antiprotozoal Agents; Antiparasitic Agents; Anti-Allergic Agents; Antimalarials; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Doxycycline; Fluticasone
• Other Study ID Numbers: GCO 14-0462

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• 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