The Role of Vitamin D in Chronic Urticaria and Angioedema Treatment

NCT ID: NCT01371877

Last Updated: 2023-09-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-01
• Study Completion Date: 2013-09-01

Brief Summary

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.

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.

Conditions

Urticaria; Angioedema; Hives; Swelling

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Vitamin D3 4000 IU

Subjects will be randomized 1:1 to high dose vitamin D defined as 4000 IU per day for 3 months.

Subjects will be given Vitamin D3 supplementation at 4000 IU daily.

Group Type: EXPERIMENTAL

High Dose Vitamin D3

Intervention Type: DRUG

Vitamin D 4000 IU per day for 3 months

Vitamin D3 600 IU

Subjects will be randomized 1:1 to low dose vitamin D as defined as 600 IU per day for 3 months.

Subjects will be given Vitamin D3 supplementation at 600 IU daily

Group Type: ACTIVE_COMPARATOR

Low Dose Vitamin D3

Intervention Type: DRUG

Vitamin D 600 IU per day

Interventions

High Dose Vitamin D3

Vitamin D 4000 IU per day for 3 months

Intervention Type: DRUG

Low Dose Vitamin D3

Vitamin D 600 IU per day

Intervention Type: DRUG

Other Intervention Names

cholecalciferol; cholecalciferol

Eligibility 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.

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Nebraska

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jill A Poole, MD

Role: PRINCIPAL_INVESTIGATOR

University of Nebraska

Locations

University of Nebraska Medical Center

Omaha, Nebraska, United States

Countries

United States

References

Thorp WA, Goldner W, Meza J, Poole JA. Reduced vitamin D levels in adult subjects with chronic urticaria. J Allergy Clin Immunol. 2010 Aug;126(2):413; author reply 413-4. doi: 10.1016/j.jaci.2010.04.040. No abstract available.

Reference Type: BACKGROUND

PMID: 20621341 (View on PubMed)

Rorie A, Goldner WS, Lyden E, Poole JA. Beneficial role for supplemental vitamin D3 treatment in chronic urticaria: a randomized study. Ann Allergy Asthma Immunol. 2014 Apr;112(4):376-82. doi: 10.1016/j.anai.2014.01.010. Epub 2014 Feb 5.

Reference Type: DERIVED

PMID: 24507460 (View on PubMed)

Other Identifiers

0271-11-FB

Identifier Type: -

Identifier Source: org_study_id