The Role of Vitamin D in Chronic Urticaria and Angioedema Treatment

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Jill Poole, MD, University of Nebraska
ClinicalTrials.gov Identifier:
NCT01371877
First received: June 1, 2011
Last updated: September 18, 2013
Last verified: September 2013
  Purpose

This clinical study was designed based on our hypothesis that vitamin D plays an important role in chronic urticaria and that high dose supplementation with vitamin D in subjects with chronic urticaria will improve clinical response.

This clinical study will investigate our hypothesis in three Specific Aims:

  1. Determine whether high dosing vitamin D supplementation (4000 IU/day) reduces medication usage (primary outcome) and urticaria severity score (secondary outcome) in subjects with chronic urticaria as compared to low dosing (600 IU/day).
  2. Determine if high dosing of vitamin D (4000 IU/day) is safe and well-tolerated in subjects with chronic urticaria with or without baseline vitamin D deficiency.
  3. Investigate whether there is an association with serum 25-hydroxyvitamin D levels, vitamin D receptor mRNA expression, and chronic urticaria severity.

Condition Intervention
Urticaria
Angioedema
Hives
Swelling
Drug: Vitamin D

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: The Role of Vitamin D in Chronic Urticaria and Angioedema Treatment

Resource links provided by NLM:


Further study details as provided by University of Nebraska:

Primary Outcome Measures:
  • Reduction in medication usage [ Time Frame: 12 week intervention ] [ Designated as safety issue: No ]
    The Unit of Measure is Efficacy. The primary outcome of this study is to determine if vitamin D supplementation reduces the medication usage in subjects with CUA. Thus, for the outcome of reduction in pills, at 12 weeks, subjects whose pill usage decreases by 2 or more pills per day will be classified as improved. Subjects whose pill consumption did not change or increased will be classified as unchanged.


Secondary Outcome Measures:
  • Change in Urticaria Severity Score [ Time Frame: 3 month intervention ] [ Designated as safety issue: No ]
    The Unit of Measure is Efficacy. The secondary outcome of this study is to determine if high dose vitamin D supplementation improves the urticaria severity score (USS). The change in USS will be compared between the groups using the independent sample t-test (assuming the distribution is normal). Logistic regression and multiple linear regression will be used to adjust for possible confounders.

  • Number of Participants with Adverse Events [ Time Frame: 3 month study trial ] [ Designated as safety issue: Yes ]
    Unit of Measure is Safety and Tolerability. The number of participants with adverse events will be compared between the groups using the independent sample t-test (assuming the distribution is normal).


Enrollment: 42
Study Start Date: November 2011
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: High Dose Vitamin D
Subjects will be randomized 1:1 to high dose vitamin D defined as 4000 IU per day for 3 months.
Drug: Vitamin D
Vitamin D 4000 IU per day for 3 months
Active Comparator: Low Dose Vitamin D
Subjects will be randomized 1:1 to low dose vitamin D as defined as 600 IU per day for 3 months.
Drug: Vitamin D
Vitamin D 600 IU per day

Detailed Description:

The purpose of this pilot, 12 week, clinical research study is to determine if supplementation with Vitamin D will improve the clinical outcome in subjects with chronic urticaria and angioedema (CUA). Vitamin D is a key element in the regulation of immune system responses, and vitamin D could play an important role in the treatment of CUA. Recently, we published that there is an important association with CUA and serum 25-hydroxy vitamin D (25OHD). Namely, vitamin D levels in subjects with CUA were significantly lower as compared to subjects with an alternative allergic disorder, allergic rhinitis. There is now one other observational report that supplementation with vitamin D (50,000/wk) in subjects CUA resulted in clinical improvement; however, there was only one treatment arm and optimal serum 25OHD required to obtain benefit was not investigated.

This current study is a double-blinded, prospective, interventional study that seeks to recruit adult subjects with physician-diagnosed CUA and randomize subjects to either the recommended dietary allowance (Vitamin D 600 IU/day) or the recommended upper limit of intake (Vitamin D 4000 IU/day). Subjects will answer a questionnaire to collect information regarding demographics, previous diagnostic tests, medications, and complete an urticaria severity score (USS). Information from the medical record: weight, height, body mass index (BMI), thyroid stimulating hormone (TSH), free thyroxine (T4), thyroid autoantibodies, urticaria autoimmune testing (CD203c results), anti-nuclear antibody (ANA), urinalysis, and allergy skin prick testing, which are part of the CUA evaluation will be obtained. Subjects will have research blood draws for serum 25OHD level, iPTH, calcium, phosphorus, albumin, urine calcium, and vitamin D receptor (VDR) gene expression. All subjects will receive standard-of-care therapy according to the 2009 Third International Consensus Meeting on Urticaria position guidelines. Follow-up visits for medication usage, urticaria severity score, and serum and urine safety monitoring will be at 6 and 12 weeks.

The hypothesis of this study is that high dosing of vitamin D will result in clinical improvement in subjects with CUA. The primary clinical endpoint is medication usage, and the secondary outcomes are urticaria severity score and prednisone rescue use. We will explore if threshold serum 25OHD levels correlate and VDR expression correlate to clinical outcomes, and to determine power analysis to conduct a larger scale study. Finally, the study aims to determine if vitamin D supplementation is safe and well-tolerated in subjects with CUA.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects will be included if they have physician-diagnosed chronic urticaria and/or angioedema (CUA). CUA is defined by having urticarial wheals (hives) and/or angioedema (dermal swelling) on a daily or almost daily for more than 6 weeks. Patients with CUA also having signs of dermatographism and/or delayed-pressure urticaria will be included in the study. Subjects with history of intolerance to non-steroidal anti-inflammatory drugs will be included but warned not to take this drug class (acetaminophen will be allowed instead).

Exclusion Criteria:

  • Subjects will be excluded if:

    1. They are not capable of answering the questionnaire.
    2. Subjects with a pure physical or allergic urticarias, and/or hereditary and acquired angioedema (C1 esterase inhibitor deficiency). These subjects will be excluded as the etiology of their disease is known.
    3. Pregnant or lactating women. All child-bearing women will be asked (verbally and on the questionnaire) if they are pregnant or lactating. If they answer yes, they will be excluded. As there is no risk or harm to the pregnant or lactating woman, a urine pregnancy test will not be used.
    4. Subjects with any clinically significant abnormality in biochemistry testing, and/or hypercalcemia (calcium > 10.3 mg/dl) or renal insufficiency (GFR< 50 ml/min).
    5. Subjects with a history of primary hyperparathyroidism, renal tubular acidosis, sarcoidosis, granulomatous disease, or malignancy.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01371877

Locations
United States, Nebraska
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198-5300
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198
Sponsors and Collaborators
University of Nebraska
Investigators
Principal Investigator: Jill A Poole, MD University of Nebraska
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Jill Poole, MD, Associate Professor, University of Nebraska
ClinicalTrials.gov Identifier: NCT01371877     History of Changes
Other Study ID Numbers: 271-11-FB
Study First Received: June 1, 2011
Last Updated: September 18, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Nebraska:
urticaria
angioedema
hive
swelling

Additional relevant MeSH terms:
Urticaria
Angioedema
Skin Diseases, Vascular
Skin Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Vascular Diseases
Cardiovascular Diseases
Vitamins
Vitamin D
Ergocalciferols
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on October 19, 2014