A Phase 2 interventional study of Sirolimus in Hereditary Hemorrhagic Telangiectasia, Nosebleeds and Epistaxis, sponsored by Unity Health Toronto. Completed at 1 site in Canada. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-06-04.
Sponsored by Unity Health Toronto · Phase 2, Interventional, and Treatment
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.
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.
106 studies on the registry are indexed under Telangiectasia, Hereditary Hemorrhagic; 24 are open to participants now.
This study's enrollment of 10 is below the median of 33 across 61 interventional studies indexed under Telangiectasia, Hereditary Hemorrhagic.
Browse Telangiectasia, Hereditary Hemorrhagic studies →Unity Health Toronto is the lead sponsor of 447 studies on the registry; 82 are open to participants now.
Of its 5 completed or terminated interventional studies of FDA-regulated products, 1 (20%) have results posted.
Counted across the registry records on this site, refreshed daily.
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.
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.
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.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
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.
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.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Reproductive potential
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
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.
All 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
Drug: Sirolimus
Oral sirolimus provided with starting dose of 2mg once daily, adjusted to maintain drug blood levels of 6-10 ng/ml (3-month course)
Electrolytes
Number of participants with clinically significant abnormal electrolytes. Electrolytes include, Sodium, potassium, chloride, total CO2
Time frame: 9 months
Hemoglobin
Number of participants with clinically significant abnormal Hemoglobin
Time frame: 9 months
Renal Function
Number of participants with clinically significant abnormal urea and creatinine
Time frame: 9 months
Liver Function
Number of participants with clinically significant abnormal AST, ALT, and total bilirubin.
Time frame: 9 months
Change in Ferritin Levels
Number of participants with clinically significant abnormal ferritin levels
Time frame: 9 months
Blood Glucose Level
Number of participants with clinically significant abnormal glucose
Time frame: 9 months
Lipid Assessment
Number of participants with clinically significant abnormal total cholesterol and triglycerides
Time frame: 9 months
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.
Time frame: 3 months
Total White Blood Cells
Number of participants with clinically significant abnormal total WBC
Time frame: 9 months
Red Blood Cells and Platelets
Number of participants with Clinically Significant RBCs and platelets
Time frame: 9 months
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).
Time frame: 9 months
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.
Time frame: 9 months
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.
Time frame: 9 months
| Milestone | Overall Study Period |
|---|---|
| Started | 10 |
| Completed | 10 |
| Not completed | 0 |
Number of participants with clinically significant abnormal electrolytes. Electrolytes include, Sodium, potassium, chloride, total CO2
| Participants | Baseline | Treatment Period | Follow-up |
|---|---|---|---|
| Electrolytes | 0 | 0 | 0 |
Number of participants with clinically significant abnormal Hemoglobin
| Participants | Baseline | Treatment Period | Follow-up |
|---|---|---|---|
| Hemoglobin | 0 | 2 | 0 |
Number of participants with clinically significant abnormal urea and creatinine
| Participants | Baseline | Treatment Period | Follow-up |
|---|---|---|---|
| Renal Function | 0 | 0 | 0 |
Number of participants with clinically significant abnormal AST, ALT, and total bilirubin.
| Participants | Baseline | Treatment Period | Follow-up |
|---|---|---|---|
| Liver Function | 0 | 0 | 0 |
Number of participants with clinically significant abnormal ferritin levels
| Participants | Baseline | Treatment Period | Follow-up |
|---|---|---|---|
| Change in Ferritin Levels | 0 | 0 | 0 |
Number of participants with clinically significant abnormal glucose
| Participants | Baseline | Treatment Period | Follow-up |
|---|---|---|---|
| Blood Glucose Level | 0 | 1 | 0 |
Number of participants with clinically significant abnormal total cholesterol and triglycerides
| Participants | Baseline | Treatment Period | Follow-up |
|---|---|---|---|
| Lipid Assessment | 0 | 0 | 0 |
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.
| Adverse Events | Oral Sirolimus Tablets |
|---|---|
| Total Number of Adverse Events (AEs) | 20 |
Number of participants with clinically significant abnormal total WBC
| Participants | Baseline | Treatment Period | Follow-up |
|---|---|---|---|
| Total White Blood Cells | 0 | 2 | 0 |
Number of participants with Clinically Significant RBCs and platelets
| Participants | Baseline | Treatment Period | Follow-up |
|---|---|---|---|
| Red Blood Cells and Platelets | 0 | 0 | 0 |
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).
| minutes | Baseline | Treatment Period | Follow-up |
|---|---|---|---|
| Change in Epistaxis Duration (PRO-CB) | 126 (28 to 339) | 144 (28 to 359) | 53 (11 to 230) |
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.
Results for this outcome have not been posted.
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.
| units on a scale | End of Baseline (Week 12) | End of Treatment (Week 24) | Follow up |
|---|---|---|---|
| Change in Epistaxis Severity Score (ESS) at Treatment and Follow-up Periods Compared to Baseline | 4.78 (3.71 to 6.45) | 4.42 (2.93 to 5.98) | 3.33 (2.25 to 5.07) |
Collected over 9 months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Oral Sirolimus Tablets | 0/10 (0%) | 0/10 (0%) | 10/10 (100%) |
| Event | Oral Sirolimus Tablets |
|---|---|
| HeadachesNervous system disorders | 4/10 |
| Upper Respiratory Tract InfectionInfections and infestations | 4/10 |
| Skin reaction/rashSkin and subcutaneous tissue disorders | 4/10 |
| Epistaxis (worsened)Respiratory, thoracic and mediastinal disorders | 3/10 |
| DiarrheaGastrointestinal disorders | 3/10 |
| Anemia (worsened)Blood and lymphatic system disorders | 2/10 |
| Low WBC countBlood and lymphatic system disorders | 2/10 |
| InsomniaPsychiatric disorders | 2/10 |
| Dry mouthGastrointestinal disorders | 2/10 |
| NauseaGastrointestinal disorders | 2/10 |
| Age, Continuous(years) | Final Analysis Population |
|---|---|
| Mean | 57 ± 9.7 |
| Sex: Female, Male(Participants) | Final Analysis Population |
|---|---|
| Female | 5 |
| Male | 5 |
| Race (NIH/OMB)(Participants) | Final Analysis Population |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 1 |
| White | 9 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
Plan to share: No
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Studies of the drug tested here: Sirolimus
Telangiectasia, Hereditary Hemorrhagic →