What side effects are associated with this type of intervention?

Tacrolimus, a calcineurin inhibitor, is being studied for the treatment of recurrent nasal hemorrhage in patients with Osler-Weber-Rendu Syndrome. Known side effects of tacrolimus and similar calcineurin inhibitors include nephrotoxicity, hypertension, hyperglycemia, neurotoxicity (tremors, headaches), gastrointestinal disturbances, and an increased risk of infections due to immunosuppression. Patients may also experience electrolyte imbalances, such as hyperkalemia and hypomagnesemia.

What prior FDA approvals exist?

There are no specific FDA-approved treatments for Osler-Weber-Rendu Syndrome (Hereditary Hemorrhagic Telangiectasia, HHT) that are directly mentioned in the provided context. However, Tacrolimus, a calcineurin inhibitor, is being studied for its effectiveness in treating recurrent nasal hemorrhage in HHT patients. This suggests a potential therapeutic role for calcineurin inhibitors in managing symptoms of HHT, although further research and clinical trials are needed to establish their efficacy and safety.

What other types of research exist?

Promising novel alternatives to Tacrolimus for HHT patients include anti-angiogenic therapies such as bevacizumab, which has shown efficacy in reducing epistaxis and gastrointestinal bleeding. Additionally, thalidomide and its analogs, which have anti-angiogenic properties, are being explored for their potential benefits in managing HHT symptoms.

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Immunosuppressant

Tacrolimus for Hereditary Hemorrhagic Telangiectasia

Phase 2

Waitlist Available

Led By Marie E Faughnan, MD,MSc,FRCPC

Research Sponsored by Unity Health Toronto

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Age > 18 years

Clinical HHT diagnosis or personal genetic diagnosis of HHT

Must not have

Specific contra-indications for study drug (detailed in the product monograph)

Acute infection

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline, weeks; 12,18,24,30,36,42,48,60,66,72,78,84,96

Awards & highlights

No Placebo-Only Group

Summary

This trial tests oral low-dose tacrolimus for patients with a condition that causes severe nosebleeds. Tacrolimus helps by reducing new blood vessel growth and inflammation, which can decrease bleeding.

Who is the study for?

This trial is for adults over 18 with Hereditary Hemorrhagic Telangiectasia (HHT) who suffer from frequent nosebleeds, at least 15 minutes per week. Participants must have a clinical or genetic diagnosis of HHT and at least one visible telangiectasia. Pregnant or breastfeeding women, those not using effective contraception, people with certain allergies, acute infections, high creatinine levels, liver issues, abnormal ECGs or unstable illnesses cannot join.

What is being tested?

The study tests if low-dose tacrolimus capsules taken orally can reduce the severity of nosebleeds in HHT patients. It will also look for changes in vascular malformations and biomarkers related to HHT in blood and tissue. This Phase II trial involves giving subjects the drug twice daily for six months.

What are the potential side effects?

Tacrolimus may cause side effects such as increased risk of infection due to immune system suppression, kidney problems reflected by elevated creatinine levels, potential liver dysfunction indicated by raised transaminase levels (AST/ALT), and possible heart rhythm abnormalities detectable on an ECG.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am older than 18 years.

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I have been diagnosed with HHT either through clinical evaluation or genetic testing.

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I have nosebleeds lasting 15 minutes or more each week.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have no known allergies or reactions to the study drug.

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I currently have an infection.

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I am not pregnant, breastfeeding, nor planning to become pregnant during the study.

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I am a man and my partner can have children but we are not using effective birth control.

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My liver enzymes are twice as high as the normal limit.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline, weeks; 12,18,24,30,36,42,48,60,66,72,78,84,96

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline, weeks; 12,18,24,30,36,42,48,60,66,72,78,84,96

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline, weeks; 12,18,24,30,36,42,48,60,66,72,78,84,96 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

The change in epistaxis (nose bleeding) severity using low-dose Tacrolimus

Secondary study objectives

Change in Biomarkers

Change in Chronic Bleeding

Change in Epistaxis Severity Score (ESS)

+2 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Tacrolimus immediate-release capsulesExperimental Treatment1 Intervention

subjects will be treated with a 6 months course of oral low-dose tacrolimus capsules to be taken twice daily starting dose of 0.025 mg/kg/day, adjusted to maintain drug blood levels of 2-5ng/ml

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Tacrolimus, a calcineurin inhibitor, works by suppressing the immune system and reducing inflammation. It inhibits the activity of T-cells, which are crucial in the immune response, thereby decreasing the production of inflammatory cytokines. This mechanism is particularly relevant for Osler-Weber-Rendu Syndrome (HHT) patients because it can help reduce the severity of recurrent nasal hemorrhages, a common and debilitating symptom of the disease. By targeting the underlying inflammatory pathways, Tacrolimus may help in managing the vascular malformations characteristic of HHT, potentially improving the quality of life for these patients.

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