AzTrials
AzTrials

Hereditary Haemorrhagic TelangiectasiaPhase 2NCT03981562

Vitamin D and Hereditary Haemorrhagic Telangiectasia

A Phase 2 study testing Vit D in people with Hereditary Haemorrhagic Telangiectasia, run by St. Paul's Hospital, Canada at 1 site in Canada.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 19 years and older
Conditions the study is for
Hereditary Haemorrhagic Telangiectasia
What is being tested?
Vit D
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
60 participants
Where
1 siteCanada
Study dates
16 Jul 2018to 1 Sep 2020
Phase
Phase 2
Are there results?
None posted in the registry

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

Who may be able to join

  • 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)

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

Amin Javer, MD FRCSCFARS contact

6048069926

sinusdoc@me.com

Canada1 site, 1 recruiting
  • E.N.T Clinic, St. Paul's Hospital

    Vancouver, British Columbia, V6Z 1Y6

    India Dhillon, BSc, 604-806-9926, idhillon3@providencehealth.bc.ca

    Amin R Javer, MD FRCSCFARS

    Recruiting

Other trials in Canada

About this study

Official title: 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.

Read the 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.

  1. 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.

Being tested
Vit D, Placebo Oral Tablet
Keywords
Epistaxis
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.

  • Vit DDrug

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

  • Placebo Oral TabletDrug

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

Study groups in NCT03981562
Study groupRoleWhat they receive
1000 IU Vitamin DExperimentalNot described
Receives: Drug: Vit D
4000 IU Vitamin DExperimentalNot described
Receives: Drug: Vit D
PlaceboPlacebo comparatorNot described
Receives: Drug: Placebo Oral Tablet

What is being measured

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

  1. Change in Epistaxis Severity Score

    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).

    Measured: Baseline, 3 months, and 6 months

Secondary outcomes (1)
  1. Change in Modified Lund-Kennedy Score

    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.

    Measured: Baseline, 3 months, and 6 months

Timeline

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

  1. First posted11 Jun 2019
  2. Study start16 Jul 2018
  3. Primary completion1 Jul 2020 (estimated)
  4. Study completion1 Sep 2020 (estimated)

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
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03981562
Sponsor's protocol ID
H18-01337
Status last verified
Jun 2019
First submitted
24 May 2019
Last updated
11 Jun 2019
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: All IPD that underlie results in a publication will be available to other researchers.

Publications

  • 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.

    PubMed 19337313
  • 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
  • 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.

    PubMed 20087969
  • 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.

    PubMed 27195194
  • 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.

    PubMed 2729347
  • 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.

    PubMed 21718915
  • 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.

    PubMed 24227938
  • 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.

    PubMed 29537299
  • 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.

    PubMed 26205234
  • 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.

    PubMed 21546842
  • 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.

    PubMed 24782401

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Vit D in people with Hereditary Haemorrhagic Telangiectasia, run by St. Paul's Hospital, Canada 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 3 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 11 Jun 2019. 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. Some participants in this study may receive a placebo. 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?

Results are not available in the source record.

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

Contact Amin Javer, MD FRCSCFARS (6048069926, sinusdoc@me.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Epistaxis Severity Score (time frame: Baseline, 3 months, and 6 months). 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 NCT03981562, which also lists 11 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 11 Jun 2019.

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