Vitamin D and Hereditary Haemorrhagic Telangiectasia

June 7, 2019 updated by: Amin Javer, St. Paul's Hospital, Canada

Vitamin D Supplementation and Reduction of Severity and Frequency of Epistaxis in Hereditary Haemorrhagic Telangiectasia

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

  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.

Study Type

Interventional

Enrollment (Anticipated)

60

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Amin Javer, MD FRCSCFARS
  • Phone Number: 6048069926
  • Email: sinusdoc@me.com

Study Locations

  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V6Z 1Y6
        • Recruiting
        • E.N.T Clinic, St. Paul's Hospital
        • Contact:
        • Principal Investigator:
          • Amin R Javer, MD FRCSCFARS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

17 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Drug: Placebo Oral Tablet
Patients will take a placebo oral tablet once a day for 6 months.
Experimental: 1000 IU Vitamin D
Drug: Vit D
Patients will take an oral vitamin D supplement once a day for 6 months.
Experimental: 4000 IU Vitamin D
Drug: Vit D
Patients will take an oral vitamin D supplement once a day for 6 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Epistaxis Severity Score
Time Frame: Baseline, 3 months, and 6 months

A questionnaire that will be given to the patients at each visit which is a major predictor of quality of life in HHT patients.

The score includes six independent predictors of self-described epistaxis severity. The responses will then be weighted by respective coefficients and these added together to give a raw ESS, which will then be divided by the range of the raw score (2.71) and multiplied by 10 to give normalized ESS within the range of 0 to 10 (no epistaxis to severe epistaxis).
Baseline, 3 months, and 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Modified Lund-Kennedy Score
Time Frame: Baseline, 3 months, and 6 months
The score is an objective measure based on Endoscopic sinonasal mucosal inflammation. The score is determined from a range of 0-12 with higher numbers indicating worse inflammation. Endoscopy will determine the density and location of telangiectasias, vascular morphology or patterns, relative percentage of arteriovenous malformations (AVMs), degree of crusting, septal perforation and site.
Baseline, 3 months, and 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

St. Paul's Hospital, Canada

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 16, 2018

Primary Completion (Anticipated)

July 1, 2020

Study Completion (Anticipated)

September 1, 2020

Study Registration Dates

First Submitted

May 24, 2019

First Submitted That Met QC Criteria

June 7, 2019

First Posted (Actual)

June 11, 2019

Study Record Updates

Last Update Posted (Actual)

June 11, 2019

Last Update Submitted That Met QC Criteria

June 7, 2019

Last Verified

June 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H18-01337

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

All IPD that underlie results in a publication will be available to other researchers.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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