Doxycycline for Hereditary Hemorrhagic Telangiectasia
HHT
Doxycycline Crossover Trial for Hereditary Hemorrhagic Telangiectasia
2 other identifiers
interventional
13
1 country
1
Brief Summary
This study will investigate the effectiveness of oral doxycycline for the treatment of recurrent nasal hemorrhage in Hereditary Hemorrhagic Telangiectasia (HHT) subjects. The primary outcome for the trials will be the reduction of epistaxis severity (minutes of bleeding per week). The biological outcomes of interest are the regression of vascular malformations as well as tissue and circulation biomarkers of the relevant mechanistic pathways. A Phase II, randomized double-blind placebo-controlled crossover trial. Approximately 30 subjects with HHT, with moderate-severe recurrent epistaxis will participate in the randomized double-blind placebo-controlled cross over trial. Subject will be treated with a 6-month course of doxycycline 100mg twice daily or placebo twice daily.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Sep 2018
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 21, 2017
CompletedFirst Posted
Study publicly available on registry
January 11, 2018
CompletedStudy Start
First participant enrolled
September 12, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 18, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2021
CompletedApril 1, 2025
March 1, 2025
2.4 years
November 21, 2017
March 26, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
The reduction in epistaxis (nose bleeding) severity over 96 weeks
Participants will be asked to maintain a daily diary for the duration of the study (96 weeks). Participants will record all epistaxis events daily, noting the duration in minutes and whether or not there was gushing during each nosebleed. The change in epistaxis severity will be measured from a sum of duration of all bleeding events each week, as measured from the participant daily diary.
daily for 96 weeks
Secondary Outcomes (5)
Change in epistaxis severity score (ESS)
baseline, week 12, week 24, week 36, week 48, week 60, week 72, week 84, week 96
Measures related to chronic bleeding by a change from baseline
Baseline, week 12, week 18, week 24, week 30, week 36, week 42, week 48, week 60, week 66, week 72, week 78, week 84, week 96
Regression of vascular malformations using Micro-imaging measures
week 12 (day 0), week 36, week 60, week 84
Elucidate the mechanisms of action of doxycycline using tissue sample
week 36, week 84
The measurement of a change in biomarkers
week 12 (day 0), week 24, week 36, week 48, week 60, week 72, week 84, week 96
Study Arms (2)
doxycycline Hyclate
ACTIVE COMPARATORsubjects will be treated with a 6-month course of doxycycline oral capsule at a dose of 100mg twice daily
Placebo
PLACEBO COMPARATORsubjects will be given a placebo oral capsule twice daily for 6-months
Interventions
Doxycycline will be given for 6 months, followed by a washout period for 6 months (pre or post a crossover intervention)
Placebo will be given for 6 months, followed by a washout period for 6 months (pre or post a crossover intervention)
Eligibility Criteria
You may qualify if:
- Age \>+ 18 years
- Clinical HHT diagnosis or genetic diagnosis of HHT
- Known personal or familial endoglin (ENG), ALK1 or SMAD4 mutation
- Epistaxis at least 15 min per week (mean for past month)
- At least two skin telangiectases
- \>2mm diameter available for excisional biopsy,
- at least two other telangiectases (skin or mucosal) available for micro-imaging
- Ability to give written informed consent
- including compliance with the requirements of the study
You may not qualify if:
- Allergy/intolerance to the study drug or related agents
- Unstable medical illness
- Acute infection
- Creatinine \> upper limit of normal (ULN)
- Liver transaminases (AST or ALT) \>= 2x ULN
- Recent (within 2 month) use of study drug or other tetracycline agents
- Women who are pregnant
- Breastfeeding
- Plan to become pregnant during of the study
- Beta human chorionic gonadotropin (BHCG) level \<6 IUL (re-test if 6-24 IU/L)
- Specific contra-indications for study drug
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Unity Health Torontolead
- Barrow Neurological Institutecollaborator
- Duke Universitycollaborator
- Feinstein Institute for Medical Researchcollaborator
- University of Pittsburghcollaborator
- Sunnybrook Health Sciences Centrecollaborator
Study Sites (1)
St. Michael's Hospital
Toronto, Ontario, M5B 1W8, Canada
Related Publications (1)
Thompson KP, Sykes J, Chandakkar P, Marambaud P, Vozoris NT, Marchuk DA, Faughnan ME. Randomized, double-blind, placebo-controlled, crossover trial of oral doxycycline for epistaxis in hereditary hemorrhagic telangiectasia. Orphanet J Rare Dis. 2022 Nov 7;17(1):405. doi: 10.1186/s13023-022-02539-8.
PMID: 36344987DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Marie E Faughnan, MD MSc FRCPC
St. Michael's Hospital / The University of Toronto
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 21, 2017
First Posted
January 11, 2018
Study Start
September 12, 2018
Primary Completion
February 18, 2021
Study Completion
March 1, 2021
Last Updated
April 1, 2025
Record last verified: 2025-03
Data Sharing
- IPD Sharing
- Will not share