A Phase 2 interventional study of Doxycycline Hyclate and Placebo in Hereditary Hemorrhagic Telangiectasia (HHT), sponsored by Unity Health Toronto. Completed at 1 site in Canada. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-04-01.
Sponsored by Unity Health Toronto · Phase 2, Interventional, and Treatment
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Among 12 studies in Telangiectasia, Hereditary Hemorrhagic with a site in Canada — 1 open to participants now, 3 under way, none of them phase 3. Telangiectasia, Hereditary Hemorrhagic · Canada.
Among the 12 studies in Telangiectasia, Hereditary Hemorrhagic with a site in Canada, this one is the 5th largest by enrollment of the 10 interventional ones that give a count, is one of 3 that started in 2018, is one of 5 in phase 2, and was the 6th registered.
106 studies on the registry are indexed under Telangiectasia, Hereditary Hemorrhagic; 24 are open to participants now.
Browse Telangiectasia, Hereditary Hemorrhagic studies →1 of the 12 studies in Telangiectasia, Hereditary Hemorrhagic with a site in Canada is open now. Recruiting first, the newest first:
Diagonal Therapeutics, Inc. · Sites in Canada, Australia, New Zealand
Ages 18+
A study can be open while its sites in Canada have not opened yet or have stopped. Only those recruiting at a site in Canada →
Of the 17 Telangiectasia, Hereditary Hemorrhagic studies recruiting now, 14 (82%) set no upper age limit and 2 (12%) stop at 75 or younger; 6 take children under 18; 3 take healthy volunteers.
This study: 18 Years and older · all sexes · no healthy volunteers.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
12 studies; the count open now beside each. This study's row is marked.
A study in two phases is counted once above. Listed by phase, each with its combined phases: Phase 1 3 · Phase 2 8
First in 2010; this study’s year is marked. 3 started in 2018.
By drug class, each counting the studies that test any of its medicines:
This study's enrollment of 13 is below the median of 33 across 61 interventional studies indexed under Telangiectasia, Hereditary Hemorrhagic.
Median enrollment 12 across the 10 interventional studies, 1,284 across the 2 observational. Of the 8 that completed or were terminated, 4 (50%) have results posted.
This tab as a report to print or save as PDF → With an account.
3 of 12 have an industry lead sponsor. The 5 most frequent:
Unity Health Toronto is the lead sponsor of 447 studies on the registry; 81 are open to participants now.
Of its 5 completed or terminated interventional studies of FDA-regulated products, 1 (20%) have results posted.
Unity Health Toronto has 8 studies filed under Telangiectasia, Hereditary Hemorrhagic — fewer than ten, so there is no comparison to draw.
1 of the studies in Telangiectasia, Hereditary Hemorrhagic with a site in Canada that are under way reach primary completion within a year, 0 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT07623525Diagonal Therapeutics, Inc.DIAG723 in Adults With Hereditary Hemorrhagic Telangiectasia | 2027-11-30 |
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Among the 12 studies in Telangiectasia, Hereditary Hemorrhagic with a site in Canada, from their registry updates:
Nothing recorded among them since 2026-09-25.
This tab as a report to print or save as PDF → With an account.
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.
The aim is to study is to evaluate doxycycline as a treatment for HHT with the proposed "HHT Clinical Trial Protocol". Rare disease presents a number of challenges in clinical trial design, including recruitment challenges, related power limitations and less knowledge about outcomes measurement. Considering these limitations, as well as the large variability in epistaxis measures across HHT patients, a crossover-trial design, with each subject receiving the study drug and placebo, and therefore serving as their own control, has been selected, including randomization and blinding, to limit bias in measuring this subjective outcome.
This study will investigate doxycycline, given its demonstrated anti-angiogenic and anti-inflammatory properties, as well as compelling effects in arteriovenous malformation (AVM) models. Doxycycline also has the advantages of a proven safety track record for long-term use, oral administration and low cost. Doxycycline suppresses vascular endothelial growth factor (VEGF)-induced cerebral matric metalloproteinase-9 (MMP-9) activity in vivo in the mouse model, and has anti-inflammatory effects as well, via inhibition of pro-inflammatory cytokines. In human brain vascular malformation tissue, there is evidence of increased expression of MMP-9 and VEGF and another tetracycline, minocycline, has attenuated brain hemorrhage in the mouse. Recently, a small retrospective case series reported sustained reduction in nasal hemorrhage in seven HHT patients treated with oral doxycycline. We hypothesize that oral doxycycline will reduce nasal hemorrhage in HHT subjects, through anti-angiogenic and/or anti-inflammatory mechanisms, both of which have been implicated in HHT.
This is a double-blind randomized placebo-controlled trial (N=30) of oral doxycycline (100mg twice daily, 6-month course) in HHT subjects with moderate-severe recurrent nasal hemorrhage. Drug dosing and safety monitoring will be tailored specifically to the agent studied. The primary outcome will be reduction of bleeding minutes per week. In addition, vascular malformation tissue (cutaneous) will be obtained pre and post-treatment, and stained for inflammatory, angiogenic and bone morphogenetic protein-9 (BMP9)-activin A receptor like type1(ALK1)-endoglin- Smad1/5/9 pathway markers. In addition, pre-excision, vascular malformations will be imaged with speckle variance optical coherence tomography (SVOCT), in vivo non-invasive micro-angiography to measure lesion structure, vessel volume and vessel density, as previously described. If the drugs studied are effective at reducing nasal hemorrhage, this will have important clinical implications for HHT patients, and the tissue and imaging may provide important insights into mechanisms.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
At least two skin telangiectases
Ability to give written
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
subjects will be treated with a 6-month course of doxycycline oral capsule at a dose of 100mg twice daily
Drug: Doxycycline Hyclate
subjects will be given a placebo oral capsule twice daily for 6-months
Drug: Placebo
Doxycycline will be given for 6 months, followed by a washout period for 6 months (pre or post a crossover intervention)
Also known as: capsule
Placebo will be given for 6 months, followed by a washout period for 6 months (pre or post a crossover intervention)
Also known as: capsule
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.
Time frame: daily for 96 weeks
Change in epistaxis severity score (ESS)
The epistaxis severity score is a six item questionnaire used to calculate a severity of HHT related nose bleeding. Each question is pertaining to the subject's typical symptoms within the last 3 months period. The first three questions are related to frequency, duration and intensity. The forth question whether or not medical attention was sought for nose bleeding. The remaining two questions are related to the presence of anemia and the need for blood transfusion due to nose bleeding. The resulting epistaxis severity score vary between; none 0-1, mild bleeding \>1-4, moderate bleeding \>4-7 and \>7-10 for severe bleeding.
Time frame: 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
Blood samples will be taken to measure change in chronic bleeding by looking at the hemoglobin, ferritin and iron saturation level. Samples will be taken prior to investigational product for a baseline value. This will be followed by measurements every six weeks during the periods of investigational product for comparative analysis.
Time frame: 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
Telangiectases will be micro-imaged using an established medical imaging technique speckle variance optical coherence tomography (SVOCT). The micro-imaging will be used for vasculature measurements. The SVOCT will measure the telangiectasia lesion area, volume, and density, lesion flow velocity and volume flow rate. Structural images will be generated. Imaging will be performed at four time points throughout the duration of the study.
Time frame: week 12 (day 0), week 36, week 60, week 84
Elucidate the mechanisms of action of doxycycline using tissue sample
A punch biopsy of one cutaneous telangiectasia will be performed at two time points during the study. The biopsy tissue sample will be taken at the end of each 6 month active comparator (drug) or placebo treatment. The tissue will be analyze for lesion vessel density, distribution of vessel types (capillary, venule, arteriole) and for insights into mechanisms. Further investigation will include staining for inflammatory, angiogenesis and BMP9-ALK1-endoglin-Smad1/5/9 pathway markers (VEGF, MMP-9, cyclooxygenase-2 (COX-2), Endoglin, ALK1).
Time frame: week 36, week 84
The measurement of a change in biomarkers
Serum, plasma levels will be measured for inflammatory, angiogenic, and BMP9-ALK1-endoglin-Smad1/5/9 pathway (VEGF, MMP-9, Thrombospondin-2, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), endothelin). Biomarker samples will be collected every 3-months. This will allow each subject to also provide their own controls for each treated case. The change in biomarkers will be analyzed.
Time frame: week 12 (day 0), week 24, week 36, week 48, week 60, week 72, week 84, week 96
Plan to share: No
Ran from Sep 2018 to primary completion in Feb 2021, 29 months.
Of 14 phase 2 interventional studies under Telangiectasia, Hereditary Hemorrhagic, half reached primary completion within 36 months of starting (the median), counting those still running; a quarter within 29 and three quarters within 55. This study's 29 months is below that.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Mar 2025. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Doxycycline
Telangiectasia, Hereditary Hemorrhagic →