AzTrials
AzTrials

Hereditary Hemorrhagic TelangiectasiaPhase 2NCT05269849

Sirolimus for Nosebleeds in HHT

A Phase 2 study testing Sirolimus in people with Hereditary Hemorrhagic Telangiectasia and Nosebleeds, run by Unity Health Toronto at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This pilot study is to determine the safety and efficacy of oral sirolimus (blood trough level 6-10ng/ml) in patients with HHT that are experiencing moderate or severe epistaxis. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Sirolimus
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
1 siteCanada
Study dates
16 Mar 2022to 2 Dec 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age > 18 years
  • Clinical HHT diagnosis (8) or genetic diagnosis of HHT
  • Epistaxis at least 15 min per week.
  • COVID-19 Vaccine (2 doses)
  • Ability to give written informed consent, including compliance with the requirements of the study.

Who cannot join

  • Allergy/intolerance to the study drug or related agents
  • Unstable medical illness
  • Acute infection
  • Creatinine > ULN (upper limit of normal)
  • Liver transaminases (AST or ALT) >= 2x ULN
  • Women participant who are pregnant or breastfeeding or plan to become pregnant during the duration of the study
Show all 12Show fewer
  • Women of childbearing potential not on effective contraception.
  • Male participants of reproductive potential whose female partners are of childbearing potential and are not planning to use highly effective contraceptive method
  • Immunocompromised
  • History of malignancy
  • Known untreated dyslipidemia (20% above the ULN of total cholesterol and triglycerides)
  • Specific contra-indications for study drug (detailed in the product monograph)

Trial locations and contacts

1 site in 1 country.

Canada1 site

  • St. Michael's Hospital

    Toronto, Ontario, M5B 1W8

Other trials in Canada

About this study

Official title: Sirolimus for Nosebleeds in HHT: A Phase II Pilot Study

This pilot study is to determine the safety and efficacy of oral sirolimus (blood trough level 6-10ng/ml) in patients with HHT that are experiencing moderate or severe epistaxis. The effect of oral sirolimus on epistaxis will be compared to baseline using the Patient-Reported Outcome of cumulative weekly nose Bleeding Duration (PRO-CB). The PRO-CB association with biomarker variability over the duration of the study will be investigated. In the pilot study subjects will be treated with 2mg of sirolimus once daily to obtain a trough level of 6-10ng/ml for 3 months.

Read the detailed description

The most common symptom of the hereditary hemorrhagic telangiectasia (HHT) disease is epistaxis. HHT is characterized by vascular (blood vessel) malformations, of the skin and mucus membranes of the nose (telangiectasia), gastrointestinal track, brain, lung and liver.

HHT is an autosomal dominant disease which is found in approximately 1 in 5000 individuals. Epistaxis affects 90% of adults with HHT, negatively affects quality of life and often causes anemia. Recent topical therapeutics trials have been negative and surgical therapies are invasive and offer only temporary benefit at best. Currently there are no highly-effective or approved systemic therapies for HHT-related epistaxis, but this is an area of active research and development. There is considerable in developing and identifying therapies that target the abnormal biology ad mechanisms in HHT, including antiangiogenic therapies, such as bevacizumab. Bevacizumab, however, is associated with significant toxicity, costly and administered intravenously.

Over the past few years, there has been considerable new evidence of the pathways involved in HHT disease and related potential therapeutic targets, including the mTOR pathway. Evidence suggests that HHT pathogenesis strongly relies on overactivated PI3K-Akt-mTOR and VEGFR2 pathways in endothelial cells. It was recently reported that the mTOR inhibitor, sirolimus, and the receptor tyrosine-kinase inhibitor, nintedanib, synergistically fully blocked, and also reversed, retinal AVMs, in the BMP9/10- immunoblocked neonatal mouse model of HHT. Subsequent unpublished preliminary data demonstrated that sirolimus was more effective than nintedanib at blocking anemia and bleeding in inducible ALK1 knockout HHT mice, and similarly effective to combined sirolimus-nintedanib. As such, sirolimus may provide therapeutic benefit for HHT patients. Human studies have shown "low-dose" sirolimus to be low risk and effective as a treatment for other vascular anomalies.

There is an urgent need for effective therapies for HHT and the chronic bleeding associated with the disease. Preliminary cellular and animal model data have identified sirolimus as a potential new pathway-based therapy in HHT. In addition, sirolimus is an interesting agent, as it is given orally and is available for repurposing. Data from other vascular malformations syndromes suggest that it can be effective in a "low-dose" range, reducing risk of toxicity, but there is only one published case report of sirolimus use in an HHT patient. This phase II pilot study will provide safety data as the primary outcome, and secondarily, efficacy data, outcome measure data and biological exploratory data, to support the planning of a future randomized and placebo -controlled clinical trial of sirolimus for epistaxis in HHT patients.

Sirolimus has been identified as a potential pathway-based therapy for HHT. Pre-clinical research has suggested that the pathogenesis of HHT is as a result of overactive mTOR and VEGFR2 pathway. Sirolimus has been found to work as an mTOR inhibitor to prevent the effects of overactive mTOR that results in arteriovenous malformations in a HHT. One clinical trial that used sirolimus to treat vascular anomalies, found that sirolimus was well tolerated and acted as an effective and safe treatment for most study participants.

Considerable experience using sirolimus in post-transplant patients and growing experience using sirolimus in patients with vascular anomalies exist. This pilot study will assess the safety and effectiveness of repurpose oral sirolimus, for epistaxis in patients with HHT.

It is hypothesized that oral sirolimus (blood trough level 6-10ng/ml) will be a safe and effective therapy for epistaxis in HHT patients.

Being tested
Sirolimus
Keywords
Hereditary Hemorrhagic Telangiectasia, HHT, Sirolimus
Medical subject headings
Telangiectasia, Hereditary Hemorrhagic, Epistaxis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SirolimusDrug

    Oral sirolimus provided with starting dose of 2mg once daily, adjusted to maintain drug blood levels of 6-10 ng/ml (3-month course)

Study groups in NCT05269849
Study groupRoleWhat they receive
All ParticipantsExperimentalAll participants received Sirolimus and were followed over the 9-month study period (3-month baseline, 3-month treatment period, 3-month follow up period). During 3-month treatment period, oral sirolimus was provided with a target blood trough of 6-10 ng/ml
Receives: Drug: Sirolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Electrolytes

    Number of participants with clinically significant abnormal electrolytes. Electrolytes include, Sodium, potassium, chloride, total CO2

    Measured: 9 months

  2. Hemoglobin

    Number of participants with clinically significant abnormal Hemoglobin

    Measured: 9 months

  3. Renal Function

    Number of participants with clinically significant abnormal urea and creatinine

    Measured: 9 months

  4. Liver Function

    Number of participants with clinically significant abnormal AST, ALT, and total bilirubin.

    Measured: 9 months

  5. Change in Ferritin Levels

    Number of participants with clinically significant abnormal ferritin levels

    Measured: 9 months

  6. Blood Glucose Level

    Number of participants with clinically significant abnormal glucose

    Measured: 9 months

  7. Lipid Assessment

    Number of participants with clinically significant abnormal total cholesterol and triglycerides

    Measured: 9 months

  8. Total Number of Adverse Events (AEs)

    Adverse events were monitored throughout the entire 9-month study period, including the 3-month baseline, 3-month treatment, and 3-month follow-up phases. However, only adverse events that occurred during the 3-month treatment period (i.e., when participants were actively receiving study drug) are reported here. This outcome measure is reporting the total number of adverse events across all participants that occurred during the 3-month treatment period.

    Adverse events were collected through patient self-reporting, clinical assessments at scheduled visits, and laboratory safety monitoring.

    Measured: 3 months

  9. Total White Blood Cells

    Number of participants with clinically significant abnormal total WBC

    Measured: 9 months

  10. Red Blood Cells and Platelets

    Number of participants with Clinically Significant RBCs and platelets

    Measured: 9 months

Secondary outcomes (3)

  1. Change in Epistaxis Duration (PRO-CB)

    Epistaxis was assessed using the Patient-Reported Outcome of Cumulative Weekly Nose Bleeding Duration (PRO-CB), collected via daily patient diary throughout the study (3-month baseline, 3-month treatment, and 3-month follow-up periods).

    Measured: 9 months

  2. Exploratory Biomarker Analysis Related to Angiogenesis and Inflammation

    Plasma samples were collected for future analysis of circulating biomarkers associated with angiogenesis and inflammation in HHT. The specific biomarker panel is to be finalized in collaboration with the HHT Study Team, and may include proteins such as ANG2, sICAM1, PIGF, TSP2, sVEGFR2, BMP9, IL-6, SDF1, sVCAM1, sVEGFR3, sCD73, sIL6R, TGF-β1, VEGF, sENG, OPN, TGF-β2, VEGF-C, GP130, PDGF-AA, sTGFβR3, VEGF-D, HGF, PDGF-BB, TIMP1, and sVEGFR1. Quantification methods (e.g., ELISA, multiplex immunoassay) and timepoints will be determined prior to analysiThis is an exploratory, post-treatment outcome measure and no data are yet available.s. This is an exploratory, post-treatment outcome measure and no data are yet available.

    Measured: 9 months

  3. Change in Epistaxis Severity Score (ESS) at Treatment and Follow-up Periods Compared to Baseline

    Epistaxis severity was measured using the Epistaxis Severity Score (ESS). ESS was administered at each clinic visit throughout the 9-month study period. However, only the ESS scores collected at Week 12 (end of baseline), Week 24 (end of treatment), and Week 36 (end of follow-up) were used for this outcome analysis. The ESS ranges from 0 to 10, with higher scores indicating more severe epistaxis.

    Measured: 9 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Mar 2022
  2. Study start16 Mar 2022
  3. Primary completion2 Dec 2024
  4. Study completion2 Dec 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Open label
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05269849
Sponsor's protocol ID
200421448
Status last verified
May 2026
First submitted
14 Feb 2022
Last updated
4 Jun 2026
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Faughnan ME, Mager JJ, Hetts SW, Palda VA, Lang-Robertson K, Buscarini E, Deslandres E, Kasthuri RS, Lausman A, Poetker D, Ratjen F, Chesnutt MS, Clancy M, Whitehead KJ, Al-Samkari H, Chakinala M, Conrad M, Cortes D, Crocione C, Darling J, de Gussem E, Derksen C, Dupuis-Girod S, Foy P, Geisthoff U, Gossage JR, Hammill A, Heimdal K, Henderson K, Iyer VN, Kjeldsen AD, Komiyama M, Korenblatt K, McDonald J, McMahon J, McWilliams J, Meek ME, Mei-Zahav M, Olitsky S, Palmer S, Pantalone R, Piccirillo JF, Plahn B, Porteous MEM, Post MC, Radovanovic I, Rochon PJ, Rodriguez-Lopez J, Sabba C, Serra M, Shovlin C, Sprecher D, White AJ, Winship I, Zarrabeitia R. Second International Guidelines for the Diagnosis and Management of Hereditary Hemorrhagic Telangiectasia. Ann Intern Med. 2020 Dec 15;173(12):989-1001. doi: 10.7326/M20-1443. Epub 2020 Sep 8.

    PubMed 32894695

  • Merlo CA, Yin LX, Hoag JB, Mitchell SE, Reh DD. The effects of epistaxis on health-related quality of life in patients with hereditary hemorrhagic telangiectasia. Int Forum Allergy Rhinol. 2014 Nov;4(11):921-5. doi: 10.1002/alr.21374. Epub 2014 Aug 21.

    PubMed 25145809

  • Whitehead KJ, Sautter NB, McWilliams JP, Chakinala MM, Merlo CA, Johnson MH, James M, Everett EM, Clancy MS, Faughnan ME, Oh SP, Olitsky SE, Pyeritz RE, Gossage JR. Effect of Topical Intranasal Therapy on Epistaxis Frequency in Patients With Hereditary Hemorrhagic Telangiectasia: A Randomized Clinical Trial. JAMA. 2016 Sep 6;316(9):943-51. doi: 10.1001/jama.2016.11724.

    PubMed 27599329

  • Shovlin CL, Guttmacher AE, Buscarini E, Faughnan ME, Hyland RH, Westermann CJ, Kjeldsen AD, Plauchu H. Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome). Am J Med Genet. 2000 Mar 6;91(1):66-7. doi: 10.1002/(sici)1096-8628(20000306)91:13.0.co;2-p.

    PubMed 10751092

  • Sadick H, Naim R, Sadick M, Hormann K, Riedel F. Plasma level and tissue expression of angiogenic factors in patients with hereditary hemorrhagic telangiectasia. Int J Mol Med. 2005 Apr;15(4):591-6.

    PubMed 15754019

  • Wetzel-Strong SE, Weinsheimer S, Nelson J, Pawlikowska L, Clark D, Starr MD, Liu Y, Kim H, Faughnan ME, Nixon AB, Marchuk DA. Pilot investigation of circulating angiogenic and inflammatory biomarkers associated with vascular malformations. Orphanet J Rare Dis. 2021 Sep 3;16(1):372. doi: 10.1186/s13023-021-02009-7.

    PubMed 34479577

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Sirolimus in people with Hereditary Hemorrhagic Telangiectasia and Nosebleeds, run by Unity Health Toronto at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Jun 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Electrolytes (time frame: 9 months). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05269849, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in