NOrth American Study for the Treatment of Recurrent epIstaxis With DoxycycLine: The NOSTRIL Trial

NCT ID: NCT04167085

Last Updated: 2022-07-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-18
• Study Completion Date: 2021-06-01

Brief Summary

The purpose of this research study is to determine whether Doxycycline can be used to control nosebleeds (epistaxis) for patients with Hereditary Hemorrhagic Telangiectasia (HHT). Patients with HHT will be randomized to one of 2 study arms: Doxycycline or Placebo for a period of 2 months followed by a 1-month washout period before switching treatments for a further 2 months period. Observation and evaluation will continue for a period of one month after treatment is completed.

Detailed Description

This study will analyze the effect of doxycycline on nosebleeds in hereditary hemorrhagic telangiectasia (HHT), a rare and debilitating medical condition. Patients with HHT have a variety of vascular abnormalities, including changes in their nasal vasculature that result in chronic, severe nosebleeds. These nosebleeds have been shown to significantly reduce the quality of life in HHT and can be severe enough to require emergent blood transfusion. Current therapies to control nosebleeds in HHT, which include both medications and surgical treatments, are inconsistently effective and associated with a variety of problematic side effects and complications.

Doxycycline is a common, FDA-approved antibiotic medication that has been used by physicians for decades. It is a safe medication that can be used on an outpatient basis for extended periods of time with minimal side effects. Recent research has shown that doxycycline is a potent inhibitor of angiogenesis, the process of new blood vessel development. Since the vascular abnormalities in HHT form due to uncontrolled angiogenesis, it follows that doxycycline may have potential in treating HHT. A growing body of research demonstrates the efficacy of doxycycline in treating a variety of vascular conditions, including cancer of the breast, duodenum, liver prostate, and lung. Our trial will be the first to analyze the efficacy of doxycycline in treating HHT epistaxis.

This a randomized, double-blind, crossover study design. Each patient will take both placebo and doxycycline. Since this is a cross-over study, half the participants will start out with taking placebo and half start with doxycyline and then switch halfway through. After a baseline observation period, participants will be given doxycycline at 100 mg twice a day, or an identical-appearing placebo, for a period of three months. Each month they will be seen be a physician, who will take a detailed clinical history and perform a physical examination. Further, each month the patient will have blood testing to assess blood loss, and fill out scientifically validated surveys to assess quality of life and the severity of bleeding. Following this three month treatment period, participants will be observed for one additional month, with one additional blood test and clinical assessment performed after this month.

Conditions

Epistaxis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Doxycycline, then Placebo

Doxycycline for a period of 2 months followed by a 1-month washout period, and then placebo for a further 2 months period followed by a 1-month washout period.

Group Type: EXPERIMENTAL

Doxycycline

Intervention Type: DRUG

Doxycycline, 100 mg twice a day for 2 months

Placebo

Intervention Type: OTHER

Matching placebo, twice a day for 2 months

Placebo, then Doxycycline

Placebo for a period of 2 months followed by a 1-month washout period, and then Doxycycline for a further 2 months period followed by a 1-month washout period.

Group Type: EXPERIMENTAL

Doxycycline

Intervention Type: DRUG

Doxycycline, 100 mg twice a day for 2 months

Placebo

Intervention Type: OTHER

Matching placebo, twice a day for 2 months

Interventions

Doxycycline

Doxycycline, 100 mg twice a day for 2 months

Intervention Type: DRUG

Placebo

Matching placebo, twice a day for 2 months

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Diagnosis of definite HHT by the Curacao criteria or genetic diagnosis of HHT
• Epistaxis severity during observation month at least moderate by Epistaxis Severity Score (ESS) evaluation
• For female participants, a negative pregnancy test at Day -1 and agree to use birth control during treatment and for 28 days following cessation of Doxycycline

Exclusion Criteria

• Use of medication(s) contraindicated with doxycycline use within 14 days prior to the study (including barbiturates, tegretol, dilantin, warfarin, isotretinoin)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of California, Los Angeles

OTHER

Sponsor Role: lead

Responsible Party

Justin McWilliams, MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

100 UCLA Medical Plaza

Los Angeles, California, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

16-001827

Identifier Type: -

Identifier Source: org_study_id