The Role of Vitamin D in Chronic Urticaria and Angioedema Treatment
The Role of Vitamin D in Chronic Urticaria and Angioedema Treatment
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.
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.
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.