Vitamin D and Hereditary Haemorrhagic Telangiectasia

NCT ID: NCT03981562

Last Updated: 2019-06-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-07-16

Study Completion Date

2020-09-01

Brief Summary

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The study aims to assess whether supplementing vitamin D in patients diagnosed with Hereditary Haemorrhagic Telangiectasia (HHT) will decrease the frequency and severity of nosebleeds these patients experience. It is hypothesized that the larger the dose of daily vitamin D given to the patients, the less frequent and less severe the nosebleeds will be.

Detailed Description

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1. Purpose:

The focus of the study is to determine if supplementing vitamin D in patients diagnosed with HHT will reduce the frequency and severity of epistaxis episodes.
2. Hypothesis:

For patients diagnosed with HHT, daily vitamin D supplementation will reduce the frequency and severity of epistaxis. Additionally, there will be a greater reduction in epistaxis frequency and severity the larger the dose of daily vitamin D supplemented
3. Justification:

Hereditary haemorrhagic telangiectasia (HHT) is a rare autosomal dominant inherited disorder of the fibrovascular tissue that causes malformation of capillaries (called "telangiectases") and/or larger blood vessels (called "arteriovenous malformations") throughout the body. The formation of these lesions ultimately result in patients experiencing increased tendency for bleeding. These lesions may present in varying locations systemically, however recurrent and severe epistaxis is the most common presentation of HHT.

Various medical and surgical treatments exist for management of HHT patients which are aimed at decreasing the frequency and severity of epistaxis episodes. These therapies include: humidification, nasal lubrication, nasal hot saline irrigation, intranasal packing, oestrogen ointment, tranexamic acid, bevacizumab systemic/topically applied, use of propranolol to lower blood pressure, electrocautery and YAG laser. Although all these various options are available, there currently is no consensus toward an optimal solution. Treatment can become especially difficult due to progressive anaemia or when anticoagulant or anti-thrombotic therapy becomes necessary. Therefore, there is a need for establishment of a safe and effective therapy.

It has been suggested that vitamin D plays a role in cardiovascular health. Vitamin D plays a key role in establishing the integrity of blood vessels as it has been shown to provide protection of the vascular wall as well has having minor anticoagulation effects. As well, observational retrospective studies have found an association between vitamin D levels and epistaxis bleeding time and severity in HHT patients, with higher serum vitamin D levels being associated with decrease epistaxis bleeding time and severity. Despite evidence of positive effect of vitamin D on HHT, currently no prospective study has been done.
4. Objectives:

Primary Objective To determine if vitamin D supplementation with 1000 IU or 4000 IU will reduce the frequency and severity of epistaxis in HHT patients.

Secondary Objective To determine the adequate dosage of vitamin D supplementation required to reduce frequency and severity of epistaxis in HHT patients.
5. Research Method

The proposed study is a prospective double-blinded, placebo controlled, randomized control trial.

All the St. Paul's Sinus Centre patients willing to participate in the study will be invited for screening. Currently, the clinic has \~60 patients with HHT; therefore the investigators hope to enrol \~20 patients in each of the three study arms.

Consenting patient will be randomized to ensure equal number of experimental and control patients are in each arm. A closed envelop system will be used to randomize participants within each arm. Patients diagnosed with HHT who are not taking vitamin D supplementation at the time of recruitment will be randomized into one of the following three groups:

1. 1000 IU/day vitamin D,
2. 4000 IU/day vitamin D, or
3. Placebo control Patients who are already taking vitamin D at the time of recruitment will be asked to stop taking the current dose of vitamin D and will be randomized into either the 1000 IU or 4000 IU arm of the study. Patients previously taking Vitamin D will not participate as placebo controls.

Upon enrolment in the study, demographic data will be obtained, including age, gender, and ethnicity. Patient's will also have baseline blood work drawn, standard of care, (full hematological profile, ferritin, aPTT, INR, serum vitamin D, IgE) and be asked to fill out a questionnaire to provide a baseline Epistaxis Severity Score (ESS). This questionnaire is routinely used to assess quality of life in HHT patients and includes six independent predictors of self-described epistaxis severity. Baseline nasal endoscopic scoring will also be performed by endoscopic imaging of the nasal cavity.

The patients will be instructed on dosing of vitamin D supplementation. Patients will continue daily supplementation for three months until the first follow up visit. At the first follow-up visit patients will again have blood work drawn, be asked to fill out the ESS questionnaire, and receive nasal endoscopic scoring.

The last follow-up visit will be at six months and a repeat of the same procedures/tests will be carried out.

6\. Statistical Analysis:

The primary outcome of this study will be the Epistaxis Severity Score (ESS), which is obtained from patient questionnaires. The secondary outcome will be the Nasal Endoscopic Score. The difference in the ESS and endoscopic score before and after supplementation within and between groups will be analyzed using paired and unpaired students t-tests based on the variance results.

Descriptive statistics (mean, median, SD) will be used to describe demographic and hematological data collected.

Conditions

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Hereditary Haemorrhagic Telangiectasia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Patients included in the study will be randomized. Block randomization will be utilized to ensure an equal number of experimental and control patients are in each arm. A closed envelope system will be used to randomize participants within each arm.
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators
The study is double blinded, the investigators and the patients throughout the data collection and data analysis period will not be aware of the vitamin D dosage given.

Study Groups

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1000 IU Vitamin D

Group Type EXPERIMENTAL

Vit D

Intervention Type DRUG

Patients will take an oral vitamin D supplement once a day for 6 months.

4000 IU Vitamin D

Group Type EXPERIMENTAL

Vit D

Intervention Type DRUG

Patients will take an oral vitamin D supplement once a day for 6 months.

Placebo

Group Type PLACEBO_COMPARATOR

Placebo Oral Tablet

Intervention Type DRUG

Patients will take a placebo oral tablet once a day for 6 months.

Interventions

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Vit D

Patients will take an oral vitamin D supplement once a day for 6 months.

Intervention Type DRUG

Placebo Oral Tablet

Patients will take a placebo oral tablet once a day for 6 months.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 19 years or older
* Definite diagnosis of HHT using the Curacao criteria;
* HHT patients already on Vitamin D supplementation (these patients will still be included since the study is examining mega-doses specifically)

Exclusion Criteria

* Patients with sinonasal tumours;
* Patients with bleeding disorders;
* Patients with serum levels of 250 or more ng/ml of vitamin D before or during the study supplementation (considered to be toxic levels)
* Patients who are unable to speak English;
* Patients who live outside B.C.
Minimum Eligible Age

19 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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St. Paul's Hospital, Canada

OTHER

Sponsor Role lead

Responsible Party

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Amin Javer

Director, St. Paul's Sinus Centre

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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E.N.T Clinic, St. Paul's Hospital

Vancouver, British Columbia, Canada

Site Status RECRUITING

Countries

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Canada

Central Contacts

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Amin Javer, MD FRCSCFARS

Role: CONTACT

6048069926

India Dhillon, BSc

Role: CONTACT

6048069926

Facility Contacts

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India Dhillon, BSc

Role: primary

604-806-9926

References

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Govani FS, Shovlin CL. Hereditary haemorrhagic telangiectasia: a clinical and scientific review. Eur J Hum Genet. 2009 Jul;17(7):860-71. doi: 10.1038/ejhg.2009.35. Epub 2009 Apr 1.

Reference Type BACKGROUND
PMID: 19337313 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10751092 (View on PubMed)

Hoag JB, Terry P, Mitchell S, Reh D, Merlo CA. An epistaxis severity score for hereditary hemorrhagic telangiectasia. Laryngoscope. 2010 Apr;120(4):838-43. doi: 10.1002/lary.20818.

Reference Type BACKGROUND
PMID: 20087969 (View on PubMed)

Chamali B, Finnamore H, Manning R, Laffan MA, Hickson M, Whelan K, Shovlin CL. Dietary supplement use and nosebleeds in hereditary haemorrhagic telangiectasia - an observational study. Intractable Rare Dis Res. 2016 May;5(2):109-13. doi: 10.5582/irdr.2016.01019.

Reference Type BACKGROUND
PMID: 27195194 (View on PubMed)

Plauchu H, de Chadarevian JP, Bideau A, Robert JM. Age-related clinical profile of hereditary hemorrhagic telangiectasia in an epidemiologically recruited population. Am J Med Genet. 1989 Mar;32(3):291-7. doi: 10.1002/ajmg.1320320302.

Reference Type BACKGROUND
PMID: 2729347 (View on PubMed)

Al Mheid I, Patel R, Murrow J, Morris A, Rahman A, Fike L, Kavtaradze N, Uphoff I, Hooper C, Tangpricha V, Alexander RW, Brigham K, Quyyumi AA. Vitamin D status is associated with arterial stiffness and vascular dysfunction in healthy humans. J Am Coll Cardiol. 2011 Jul 5;58(2):186-92. doi: 10.1016/j.jacc.2011.02.051.

Reference Type BACKGROUND
PMID: 21718915 (View on PubMed)

Min B. Effects of vitamin d on blood pressure and endothelial function. Korean J Physiol Pharmacol. 2013 Oct;17(5):385-92. doi: 10.4196/kjpp.2013.17.5.385. Epub 2013 Oct 17.

Reference Type BACKGROUND
PMID: 24227938 (View on PubMed)

Weber LM, McDonald J, Whitehead K. Vitamin D levels are associated with epistaxis severity and bleeding duration in hereditary hemorrhagic telangiectasia. Biomark Med. 2018 Apr;12(4):365-371. doi: 10.2217/bmm-2017-0229. Epub 2018 Mar 14.

Reference Type BACKGROUND
PMID: 29537299 (View on PubMed)

Geisthoff UW, Nguyen HL, Roth A, Seyfert U. How to manage patients with hereditary haemorrhagic telangiectasia. Br J Haematol. 2015 Nov;171(4):443-52. doi: 10.1111/bjh.13606. Epub 2015 Jul 23.

Reference Type BACKGROUND
PMID: 26205234 (View on PubMed)

McDonald J, Bayrak-Toydemir P, Pyeritz RE. Hereditary hemorrhagic telangiectasia: an overview of diagnosis, management, and pathogenesis. Genet Med. 2011 Jul;13(7):607-16. doi: 10.1097/GIM.0b013e3182136d32.

Reference Type BACKGROUND
PMID: 21546842 (View on PubMed)

Reh DD, Yin LX, Laaeq K, Merlo CA. A new endoscopic staging system for hereditary hemorrhagic telangiectasia. Int Forum Allergy Rhinol. 2014 Aug;4(8):635-9. doi: 10.1002/alr.21339. Epub 2014 Apr 29.

Reference Type BACKGROUND
PMID: 24782401 (View on PubMed)

Related Links

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http://emedicine.medscape.com/article/2048472-overviw#a5

Osler- Weber-Rendu Disease (Hereditary Hemorrhagic Telangiectasia).

http://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/

Vitamin D: fact sheet for health professionals.

Other Identifiers

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H18-01337

Identifier Type: -

Identifier Source: org_study_id

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