A Randomised Controlled Trial to Evaluate the Effect of Vitamin D Supplementation in Patients With Chronic Urticaria
Phase: PHASE4
Conditions: Urticaria, Vitamin D Deficiency
Sponsor: Post Graduate Institute of Medical Education and Research, Chandigarh

Title: A trial to evaluate the effect of Vitamin D 
supplementation in patients with Chronic Urticaria 
 
Institutional ethics committee approval number: INT/IEC/2017/1314 
 
Date: Study start date- 15 July, 2019 
Protocol date: 16 June, 2019 
Expected completion date: 28 December, 2019 
 
Principal Investigator: 
 1 Dr Davinder Prasad, Professor , Department of Dermatology, Venereology,& Leprology, 
PGIMER, Chandigarh  
Co-investigator: Dr. Sendhil Kumaran, Associate Professor, Department of Dermatology, 
Venereology & Leprology, PGIMER, Chandigarh 
 
 
 
 
 
 
 
 

Title: A trial to evaluate the effect of Vitamin D 
supplementation in patients with Chronic Urticaria 
 
Summary of proposed research 
Chronic urticaria (CU) is a characterized by recurrent, raised, pruritic wheals lasting for more 
than 6 weeks, for at least 2 or more times per week and may be accompanied by angioedema in 
30-60% patients. Lifetime prevalence of CU is approximately 1.8% in general population, (1) 
with a point prevalence rate of 0.6-0.8% in adults [2] and affecting females more often than 
males. [2,3]Chronic spontaneous urticaria (CSU) is diagnosed after excluding all causes of 
physical urticaria and in most cases there is no definite cause. Antihistamines constitute the 
mainstay of therapy in CSU. Second line drugs include systemic corticosteroids, anti-
leukotrienes, hydroxychloroquine, cyclosporine, dapsone and omalizumab.[4] 
 
Vitamin D (Vit D), is a fat soluble vitamin having endocrine, paracrine and autocrine functions 
produced in the skin after ultraviolet radiation exposure or obtained from diet and supplements. 
Apart from its effect on bone and mineral metabolism, it exerts several immunomodulatory 
actions in both innate and adaptive immunity via Vit D receptors present on almost all cells. [5,6]  
 
Vit D deficiency/insufficiency has been implicated in increasing the incidence and severity of 
various immuno-inflammatory diseases like psoriasis, atopic dermatitis etc. Various authors have 
found correlation between presence of type 1 hypersensitivity diseases like asthma, atopic 
dermatitis, rhinosinusitis, food allergy and Vit D deficiency as it  is known to extensively 

influence proliferation, survival, differentiation, and function of mast cells. [7,8] Few studies have 
also suggested that Vit D inhibits development of allergic diseases and can be a potential 
treatment for allergy.[9] Various studies have shown beneficial effect of vitamin D 
supplementation in urticaria disease in other populations. [10-12] However the role of Vit D in 
urticaria is inconclusive in our population with whatever limited studies are available in 
literature. Thus we wanted to see the effect of serum Vit D supplementation  in course of CSU in 
our urticaria patients. 
 
Review of literature 
 
In a study done by Rorie A et al in 2014 [13] they reported significant decrease (40%) in total 
urticaria severity scores (USS) in the high, but not low, vitamin D3 treatment group by week 12. 
Compared with low treatment, the high treatment group demonstrated a trend (P< .052) toward 
lower total USS scores at week 12, which was driven by significant decreases in body 
distribution and number of days with hives. Beneficial trends for sleep quality and pruritus 
scores were observed with high vitamin D3. Serum 25-hydroxyvitamin D levels increased with 
high vitamin D3 supplementation, but there was no correlation between 25-hydroxyvitamin D 
levels and USS scores. 
 
In another study by Topal IO et al [14] they reported serum 25(OH)D concentration was 
significantly lower in CSU group compared to healthy subjects (p50.001). The prevalence of 
vitamin D deficiency (<20 (mg/L) and insufficiency (<30 mg/L) was significantly higher in CSU 
patients than control groups. In addition, 25(OH)D concentrations were significantly lower in 

both mild-moderate and severe CSU patients than those of the controls (p<0.011 and p50.001, 
respectively). Ninety eight percent of patients (25(OH)D <30 mg/L) were treated with vitamin 
D3 (300 000 IU/month) supplementation, and after 12 weeks, these patients showed significant 
improvements in UAS4 and CU-Q2oL scores. Conclusion: This study support the contributing 
and beneficial effects of vitamin D in the treatment of CU. Replacement of vitamin D may 
provide improvement in both the severity of symptoms and the quality of life scores in these 
patients 
 
In another recent study by Rasool R et al in 2015, [15]they evaluated role of Vitamin D 
supplementation D urticaria patients and reported low serum levels of 25 (OH)2D was observed 
in 91% of CU patients and 64% of the healthy controls (P < 0.0001). Visual analogue score 
(VAS) and 5-D itch Score in subgroups Vitamin D, antihistamincs  and VD + antihistamines + 
steroids decreased significantly from 6.7 ± 0.043, 6.6 ± 0.42 and 6.68 ± 0.40 at baseline to 5.2 ± 
0.70 (P = 0.0088), 3.3 ± 0.50 (P < 0.0001) and1.86 ± 0.39 (P < 0.0001) after treatment and from 
14.5 ± 0.72, 13 · 9 ± 0.77 and 13.9 ± 0.221 to 12.06 ± 1.10 (P = 0.0072), 8.1 ± 1.13 (P < 0.0001) 
and 5.01 ± 0 · 94 (P < 0.0001) respectively. 
 
METHODOLOGY  
 
Aims and Objectives 
Aim of the study the role of vitamin D supplementation in patients with chronic urticaria 
 
Primary Objectives’ 

1. To study Vitamin D deficiency in patients with Chronic urticaria as compared to controls 
2. To compare factors associated with vitamin D deficiency in patients of chronic urticaria 
Secondary objective 
To study the effect of vitamin D supplementation in patients of chronic Urticaria  
Materials and methods 
Sample size: Three hundred patients with chronic urticaria and 300 healthy controls   
Sampling method: Convenient sampling 
Study population: 
Study populations consisted of CSU patients and age and sex matched healthy controls having 
same Fitzpatrick skin type IV and V 
Inclusion criteria  
Adults (>18 years) having history of urticaria at least 2 days per week for 6 weeks or longer 
with/without angioedema and healthy adult controls. 
 Exclusion criteria  
1. Patients with  pure physical urticaria, only dermatographism, urticarial vasculitis, 
hereditary or acquired angioedema 
2. Patients with BMI>25 kg/m2 , dyslipidemia, diabetes, hypertension, pre-existing 
cardiovascular disease, cerebro-vascular accidents, smokers, and other systemic or 
cutaneous disorders including atopic dermatitis, psoriasis etc 
3. Patients with hypercalcemia (>11 mg/dL), renal insufficiency, hepatic disorders, 
hyperparathyroidism, sarcoidosis, other granulomatous disorders, malignancy.  
Recruitment of cases and controls to be done simultaneously in summer over a period of 3 
months.  

 
Clinical and laboratory analysis 
Each patient will undergo investigations including: routine laboratory tests (full blood count, 
urine analysis, serum glucose, hepatic functions, and creatinine, ESR, eosinophil, and total IgE), 
antinuclear and antithyroid microsomal antibodies, thyroid function tests, chest X-ray and 
abdominal ultrasonography. Additionally, dental, and ENT consultations as well as the 
autologous serum skin test (ASST) and autologous plasma skin test (APST) [10].  
 
Data Collection 
Blood will be collected at enrollment and at 0, 6- and 12-week clinic visits and processed at the 
institution’s clinical laboratory for serum Vit D, calcium, albumin, phosphorus, creatinine, serum 
urea nitrogen, inorganic phosphorus, and intact parathyroid hormone for study and safety end 
points. Spot urine for urine calcium will also be collected for safety end points. Serum Vit D 
concentration will be measured with the use of an automated direct Electrochemiluminescence 
immunoassay (Elecsys, Roche Diagnostic, Mannheim, Germany). To assess the Vit D status, the 
subjects will be divided into four groups according to serum Vit D levels: deficient (<10 ng/ml), 
very low (10-19 ng/ml), insufficiency (between 20 and 29 ng/ml), and sufficiency/normal (≥30 
ng/ml)17 
 
Assessing severity 
The urticaria activity score over 4 days (UAS4) will be used to assess the disease severity using 
number of wheals and pruritus intensity based on the EAACI/GA2LEN/EDF guidelines.[16] The 

patient’s disease severity levels  to be graded as mild (0-8), moderate (9-16), and severe (17-24). 
[17]. 
Study Design 
This is a prospective, randomized, single center clinical study. Serum Vit D level will be 
assessed in all patients at baseline. Patient with Vit D level ≥30 will be excluded from the trial 
but included in the study and those with Vit D level <30 will be randomized into 3 groups A,B 
and C. The randomization method is to done using randomized blocks with block sizes of 3 and 
6 to ensure a balance in treatment assignment over time. The randomization list is to be 
generated by computer generated table. Patients with Vit D level ≥30 will be categorized into 
Group D. Patients belonging to Group A will be treated with low dose Vit D (2000 IU/day) 
according to Indian council of medical research (ICMR) guidelines. Those in Group B will be 
treated with high dose Vit D (60,000 IU/week) and group C will not be given any Vit D 
supplements. Patients belonging to Group A and B will be treated for 12 weeks in order to safely 
restore Vit D and achieve a steady state. In addition levocetrizine 10 mg will be given to all 
patients in groups to control urticaria symptoms. All patients were treated according to 
EAACI/GA2LEN/EDF guidelines [16]. Subjects will also be provided with rescue prednisone use 
for intolerable or uncontrolled symptoms. At 6 weeks and 12 weeks, a physician assessment 
(physician blinded to treatment arm) will be conducted to check if patients had intolerable 
symptoms or took rescue prednisolone 40 mg therapy. Safety monitoring will be completed 
throughout the entirety of the study. Specific stopping rules and discontinuation of the study 
include pregnancy, a serum Vit D level higher than 100 ng/mL, or a serum calcium level higher 
than 11 mg/dL. Patients will be followed for 2 weeks after the study completion and thereafter 
data analysis will be done in 3 steps: 

Step 1: Comparison of serum Vit D level in CSU patients vs. controls 
Step 2: Assessment of factors associated with Vit D deficiency in urticaria patients 
Step 3: Effect of Vit D supplementation (group A (low dose), group B (high dose), group C(no 
supplementation) on urticaria severity using UAS4 
 
Statistical analysis: 
 The statistical analyses will be performed with the help of SPSS statistical software, version 
20.0, IBM SPSS, version 20 (SPSS, Inc., Chicago Il, USA), P<0.05 as significant. For normally 
distributed data means will be compared using unpaired t-test for two groups.  For skewed data 
Mann-Whitney test will be applied.  For categorical variables number and percentages will be 
calculated. Chi-sq test or Fisher’s exact test will be applied for categorical data. Comparison of 
serum Vit D level in CSU patients vs. controls will be performed using t-test. Assessment of 
factors associated with Vit D deficiency in urticaria patients will be performed using multi-
variate regression analysis and effect of Vit D supplementation (group A (low dose), group B 
(high dose), group C(no supplementation) on urticaria severity using UAS4 will be assessed 
using ANOVA. 
 
Primary Outcome 
1. To compare the Vitamin D deficiency in chronic urticaria patients vs controls 
2. To compare the effect of vitamin D supplemtation in patients of chronic urticaria 
 
Ethical justification: 

This is randomized controlled prospective study to evaluate the role of Vitamin D in chronic 
urticaria. In this study we are treating only patients with low vitamin D  (<30mg/ml) with 
Vitamin D supplementation and studying its effect on urticaria severity. Patients with normal 
vitamin D (>30ng/ml) are not treated. Also no patient is denied treatment as all patients are 
treated with antihistaminics. No additional treatment is given to patients. Urticaria treatment is 
done in accordance with EACCI/GA2LEN international guidelines. [16] Regular Vitamin D, PTH, 
S. Calcium and phosphate analysis is done to avoid any risk of hypervitaminosis.. All the 
investigations mentioned are routinely done in urticaria clinic as per EACCI/GA2LEN [16] 
international urticaria guidelines. This study will help us if vitamin D supplementation will help 
in better control of urticaria symptoms. All the investigations mentioned are routinely done in 
urticaria clinic as per EACCI/GA2LEN international urticaria guidelines 
 
References 
1. Khan 
DA. 
Chronic 
urticaria: 
diagnosis 
and 
management. 
Allergy 
Asthma 
Proc.2008;29:439e446. 
2.  Zazzali JL, Broder MS, Chang E, Chiu MW, Hogan DJ. Cost, utilization, and patterns of 
medication use associated with chronic idiopathic urticaria. Ann Allergy Asthma 
Immunol. 2012;108:98e102. 
3.  Sanchez-Borges M, Asero R, Ansotegui IJ, et al. Diagnosis and treatment of urticaria 
and angioedema: a worldwide perspective. World Allergy Organ J. 2012;5:125e147. 
4. Maurer M, Rosen K, Hsieh HJ, et al. Omalizumab for the treatment of chronic idiopathic 
or spontaneous urticaria. N Engl J Med. 2013;368:924e935. 

5. Holick MF. Vitamin D status: measurement, interpretation, and clinical application. Ann 
Epidemiol. 2009;19:73e78 
6. Ross AC, Manson JE, Abrams SA, et al. The 2011 report on dietary reference intakes for 
calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J 
Clin Endocrinol Metab. 2011;96:53e58. 
7. Hata TR, Kotol P, Jackson M, et al. Administration of oral vitamin D induces cathelicidin 
production in atopic individuals. J Allergy Clin Immunol. 2008;122:829e831 
8. Samochocki Z, Bogaczewicz J, Jeziorkowska R, et al. Vitamin D effects in atopic 
dermatitis. J Am Acad Dermatol. 2013;69:238e244.  
9. Goetz DW. Vitamin D treatment of idiopathic itch, rash, and urticaria/ angioedema. 
Allergy Asthma Proc. 2010;31:158e160 
10. Thorp WA, Goldner W, Meza J, Poole JA. Reduced vitamin D levels in adult subjects 
with chronic urticaria. J Allergy Clin Immunol. 2010;126:413; author reply 413e414. 
11. Goetz DW. Idiopathic itch, rash, and urticaria/angioedema merit serum vitamin D 
evaluation: a descriptive case series. W V Med J. 2011;107:14e20. 
12. Sindher SB, Jariwala S, Gilbert J, Rosenstreich D. Resolution of chronic urticaria 
coincident with vitamin D supplementation. Ann Allergy Asthma Immunol. 
2012;109:359e360 
13. 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 

14. Oguz Topal I, Kocaturk E, Gungor S, Durmuscan M, Sucu V, Yıldırmak S. Does 
replacement of vitamin D reduce the symptom scores and improve quality of life in 
patients with chronic urticaria? J Dermatolog Treat.2016;27(2):163-6.  
15. Rasool R,  Masoodi KZ,  Shera IA,  Yosuf Q,  Bhat IA,  Qasim I,Saniya Nissar S,  Shah 
ZA. Chronic urticaria merits serum vitamin D evaluation and supplementation; a 
randomized case control study World Allergy Organ J 2015; 8(1): 15. 
16. Jariwala SP, Moday H, de Asis ML, et al. The Urticaria Severity Score: a sensitive 
questionnaire/index for monitoring response to therapy in patients with chronic urticaria. 
Ann Allergy Asthma Immunol. 2009;102:475e482 
17. Zuberbier T. A summary of the new international EAACI/GA2LEN/EDF/WAO 
guidelines in urticaria. World Allergy Organ J. 2012;5(suppl 1):S1eS5. 
 
 
 
 
 
 
 
 
 
 
 
 
 

Case record form 
 
Name:                                                                                              CR No: 
Age/Sex: 
Address: 
Phone No: 
 
Chief Complains 
 
History: 
Age of onset: 
Symptoms:- 
Angioedema (Yes/NO) 
Family history of Atopy-(Yes/NO) 
Thyroid abnormalities- – Present/Absent 
Family history of similar disease- (Yes/NO) If yes then in whom 
Any other systemic illness-  
H/o any drug intake– Present/ Absent 
Duration of Sun exposure per day- (<30 min, 30min-1 hour, 1-1.5 hours, 1.5-2 hours, >2 hours)  
-  
General Physical Examination 
Height-                                                   Weight                                      BMI- 
Pulse:                      
 
BP: 
 
 
 
RR-  
 
 
Temp- 
Baseline UAS-  
Clinical signs suggestive of Atopy: 
Investigation (with date) 
full blood count 
 urine analysis 
serum glucose 
LFT 
RFT 

ESR 
total IgE 
S.Vit D level- 
S.PTH- 
S.Ca-  
S.PO4-  
ANA  
antithyroid microsomal antibodies 
 Thyroid function tests 
 chest X-ray 
Autologous serum skin test (ASST) and autologous plasma skin test (APST)  
Urine routine and microscopy:  
Investigations 
0 weeks 
6 weeks 
12 weeks 
18 weeks 
 Vit D 
 
 
 
 
S. calcium 
 
 
 
 
S. phosphorus, 
 
 
 
 
intact parathyroid hormone   
 
 
 
Spot urine for calcium 
 
 
 
 
 
Treatment given 
 
 
Next Follow up 
 
UAS at 6 weeks 
UAS at 12 weeks 
UAS at 18 weeks 
 
 
 
 
 
 

 
IEC Assent Form 
PROTOCOL NO: 
SPONSOR: 
PRINCIPAL INVESTIGATOR: Dr. M.Sendhil Kumaran 
Name of Participant:  
Title: - A randomized controlled trial to evaluate the effect of Vitamin D supplementation 
in patients with  Chronic Urticaria 
 
We are doing a research study. I am your doctor and principal investigator –Dr.M. Sendhil 
Kumaran  
 
We are doing this study to find out the effect of Vitamin D supplementation on chronic urticaria 
which will allow us to control the disease more effectively  
 
We are asking you to take part in this study because you  it is a common disease and it will help 
us in treating Vitamin D deficiency in you as well. But we will only take you if you allow us. If 
you do not want to do so your treatment will continue as usual. If you decide to take part now but 
wish to discontinue later, you can tell us and we will take you out of the study.  
 
Once you agree to take part, you will have to undergo Blood sample for biochemistry (S. Vit D, 
PTH, Ca, PO4,ALP), Urine sample (Urine Ca, creatinine) The clinical examination, 
investigations to be done are safe and standard. They are routinely done in urticaria clinic as part 
of our treatment protocol 
 
It is possible that the study will help you feel better. It can also occur that you do not get any 
benefit but the information we get from you may help other children in future.  
We have asked your parents [or guardian] their permission and it is all right with them. Do not 
hesitate to ask questions. You can also ask us about anything later on if there are no questions 
right now.  
 
 
 

Assent form 
 
 
Child's signature 
 
 
I have been explained about the study and I agree to take part in it. 
 
 
 
Child’s Name:  
Date: 
 
Certificate by the Investigator (his/her representative obtaining assent) : 
 
Tick one Signature of the 
Investigator / 
representative 
 
The child can read the assent form and was able to understand it  
 
 
 
 
The child was not capable of reading the assent form, but I verbally 
explained the information.  
 
 
 
 
Name of Investigator / representative:  
Date:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
Participant Information Sheet (PIS)  
 
PROTOCOL NO: 
SPONSOR: 
PRINCIPAL INVESTIGATOR: Dr. M.Sendhil Kumaran 
Name of Participant:  
Title:  
1. You are invited to take part in this research study. The information in this document is 
meant to help you decide whether or not to take part. Please feel free to ask if you have 
any queries or concerns. 
 
2. What is your expected duration of the participation? 
Your participation in this study will last for a total of  18 weeks 
 
3. What procedures will be followed during this study? 
You will have to undergo Blood sample for biochemistry (S. Vit D, PTH, Ca, PO4,ALP, 
VIT D polymorphism), Urine sample (Urine Ca, creatinine)  
 
4. What are the risks and discomforts to you? 
The clinical examination, investigations to be done are safe and standard. Taking blood 
sample for biochemical analysis may cause slight pain but is routinely done as part of 
urticaria management  
 
5. What benefits are expected from this research? 
  This study will help us in Vitamin D deficiency in patients of chronic urticaria and factors 
associated with it. It will also help in finding out if vitamin D supplementation improves 
urticaria control in patients. 
 
6. What are the alternatives available to you? 
You will only be given vitamin D supplemtation if your vitamin D level is low 
(<30ng/ml) and rest care will the same as other patients. Antihistamincs will be given to 
you for the urticaria disease control 
 
7. Are the data/records of the participant kept confidential? 
You have the right to confidentiality regarding the privacy of your medical information 
(personal details, results of physical examinations, investigations, and your medical history). 
By signing this document, you will be allowing the research team investigators, other study 
personnel, sponsors, institutional ethics committee to view your data, if required. 
 
8. What will be the treatment schedule(s)? 
If you participate in the study you will be given Vitmain D supplementation in addition to 
levocetrizine for 12 weeks. Thereafter supplementation will be stopped and only 

antihistaminics will be continued for the disease control 
 
9. What compensation and/or treatment(s) are available to the Participant in the event 
of a trial-related injury? 
No compensation will be awarded however in the eventuality of any trial related injury 
(which is unlikely) you will be given treatment at PGIMER at no additional costs.  
 
10. Whom to contact for trial related queries and what are the rights of Partcipants in 
the event of any injury?  
You can contact the Prinicipalinvestigator(Dr M.Sendhil Kumaran) in the event of any 
injury. 
11. Are the participants paid to take part in this study? 
No payments will be given for participation in the study 
12. What are your responsibilities during participation in the study?  
 You will be required to come for the investigations and follow up as per treatment 
schedule. You will be called for 6 weekly follow up till completion of  trial (18 weeks) 
and therafter as per your regular clinic scheduled visits 
 
13. Participation is voluntary, that the Participant can withdraw from the  study at any time 
and that refusal to participate will not involve any penalty or loss of benefits to which the 
Participant is otherwise entitled. 
 
14. Participant or Participant's representative will be notified in a timely manner if significant 
new findings develop during the course of the research which may affect the Participant's 
willingness to continue participation will be provided. 
 
15. If the participant is unable to come for follow up then his/her participation may be 
terminated by the Investigator without the Participant's consent.  
 
16. There will be no additional costs to the Participant that may result from participation in 
the study. 
 
 
17. Approximate number of Participants enrolled in the study- 300 
 
18. Any other pertinent information- No 
 
Contact persons:  
For further information / questions, you can contact us at the following address: 
 
Principal Investigator:  
Dr. M. Sendhil Kumaran 
Associate Professor 

Dept. of Dermatology, Venereology & Leprology 
Tel: 
Co-Investigator 
Prof. Dr. Davinder  Prasad 
Head of Department, Dept. of Dermatology, Venereology & Leprology 
Contact person(s): 
Dr. M.Sendhil Kumaran 
Associate Professor 
Dept. of Dermatology, Venereology & Leprology 
Email: drsen_2000@yahoo.co.in 
Tel: 8872004023 
 
In case of conflicts, you can contact the chairperson (convener) of our institutional ethics 
committee at the following address: 
Convener/Chairperson, Institutional Ethics Committee 
PGIMER, Chandigarh 
Telephone: ................ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Informed Consent Form (ICF) 
 
Study Title:  A randomized controlled trial to evaluate the effect of Vitamin D 
supplementation in patients with  Chronic Urticaria 
 
 
 
Study Number (if any): 
Subject’s Initials: _______________ 
Subject’s Name:_______________ 
Date of Birth / Age: _________________ 
 
 
Participant's 
initial  
 
 
1. I confirm that I have read and understood the information sheet dated _ _ _ _  
for the above study and have had the opportunity to ask questions. 
 
 
2. I understand that my participation in the study is voluntary and that I am      
free to withdraw at any time, without giving any reason, without my      
medical care or legal rights being affected.  
 
3.   I understand that the Sponsor of the clinical trial, others working on the      
Sponsor’s behalf, the Ethics Committee and the regulatory authorities          
will not need my permission to look at my health records both in respect        
of the current study and any further research that may be conducted in          
relation to it, even if I withdraw from the trial. I agree to this access.         
However, I understand that my identity will not be revealed in any          
information released to third parties or published. 
 
4. I agree not to restrict the use of any data or results that arise from this     
study provided such a use is only for scientific purpose(s)  
 
5. I agree to take part in the above study  
 
 
Signature (or Thumb impression) of the Subject/Legally Acceptable 
Representative:_____________ 
Date: _____/_____/______ 
Signatory’s Name: ________________________________________ 
Signature of the Investigator: ____________________________ Date:_____/_____/______ 
Study Investigator’s Name: ___________________________________ 
 
 
 

 
 
1. No such/similar study has been conducted in the department  
2. Role of Vitamin D in chronic urticaria has been proven in case series and few studies. 
However randomized controlled trials are lacking. Hence Serum vitamin D level 
assessment and supplementation is routinely done in urticaria clinic of our department of 
Dermatology but as far as assessing the improvement in severity of urticarial post 
Vitamin D supplementation hasn’t been noted by us. This study will help us in 
formulating Vitamin D supplementation protocol in urticaria clinic patients. 
 
3. Vitamin D supplementation will be done in all control patients also after 12 weeks, once 
the study period gets over, because they are in turn chronic urticarial patients. 
 
4. Sample size calculation, assuming α=0.05 and power (1-β)= 0.8 and p 1 = expected 
proportion of the outcome in group 1= 0.7 and p 2 = expected proportion of the outcome 
in group 2= 0.8, based on previous studies quoted in the protocol and on adjustment for 
size for attrition rate, the sample size (N) has to be multiplied by the correction factor 
100/100-X, where X = dropout rate in percentage (%).Lehr's formula is a quick 
calculation of sample size for power of 80% and a two-tailed significance level of 0.05. 
The required size of each of two equal groups is 16/δ2. Estimated sample size is 136 and 
with 10% drop out rate it is 149 so we have included 150 patients in both groups 
 

5. Since vitamin D assessment is done for all urticaria patients in clinic this will be a routine 
evaluation for them. In addition we plan to submit it for grant approval once ethics 
committee approval is given 
 
6. Yes, all the investigations done  are routinely done at the same frequency as proposed in 
the study based on previous studies which have been quoted in the protocol. All patients 
with deficient level will be treated, controls will also be treated after 12 weeks once gets 
period is over 
 
7. Separate information sheet for controls attached with this form. Controls will be from 
department of dermatology with diseases other than urticaria.  
 
8. Ethical justification: This is randomized controlled prospective study to evaluate the role 
of Vitamin D in chronic urticaria. In this study we are treating patients with low vitamin 
D (<30mg/ml) with Vitamin D supplementation and studying its effect on urticaria 
severity. Patients with normal vitamin D (>30ng/ml) are not treated. Also no patient is 
denied treatment as all patients are treated with antihistaminics to control urticaria 
symptoms. This study will help us if vitamin D supplementation will help in better 
control of urticaria symptoms. Urticaria treatment is done in accordance with 
EACCI/GA2LEN international guidelines. Regular monitoring of Vitamin D, PTH, S. 
Calcium and phosphate analysis is done to avoid any risk of hypervitaminosis. All the 
investigations mentioned are routinely done in urticaria clinic as per EACCI/GA2LEN 
international urticaria guidelines. 

9. Information sheet attached in all details 
10. All investigators are from urticaria clinic as they will be able to assess the disease control 
and urticaria activity once patients come for follow up. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Participant Information Sheet (PIS) for Urticaria patients 
 
PROTOCOL NO: 
SPONSOR: 
PRINCIPAL INVESTIGATOR: Dr. M.Sendhil Kumaran 
Name of Participant:  
Title:  
19. You are invited to take part in this research study. The information in this document is 
meant to help you decide whether or not to take part. Please feel free to ask if you have 
any queries or concerns. 
 
20. What is your expected duration of the participation? 
Your participation in this study will last for a total of 18 weeks.  
 
21. What procedures will be followed during this study? 
You will have to undergo Blood sample for biochemistry (S. Vit D, PTH, Ca, 
PO4,ALP),Urine sample (Urine Ca, creatinine) at 0, 6 and 12 weeks. After S. Vitamin D 
assessment at 0 weeks, patients with Serum Vit D level<30 ng/ml will be divided into 
three groups A,B and C and treated with high dose (60,00IU/week), low dose (2000 
IU/day) and no supplementation for 12 weeks. This will be done randomly without any 
bias. Once patient is allotted to one particular group he will be treated according to the 
protocol of that group as described above and above mentioned investigations will be 
done at 0,6 and 12 weeks. After 12 weeks all patients with vitamin D level <30 ng/ml 
will be treated with 60,000IU/week till level becomes normal.  
 
22. What are the risks and discomforts to you? 
The clinical examination, investigations to be done are safe and standard. Taking blood 
sample for biochemical analysis may cause slight pain but is routinely done as part of 
urticaria management  
 
 
23. What benefits are expected from this research? 
  This study will help us in Vitamin D deficiency in patients of chronic urticaria and factors 
associated with it. It will also help in finding out if vitamin D supplementation improves 
urticaria control in patients. 
 
24. What are the alternatives available to you? 
You will only be given vitamin D supplementation if your vitamin D level is low 
(<30ng/ml) and rest care will the same as other patients. Antihistamines will be given to 
you for the urticaria disease control 
 
25. Are the data/records of the participant kept confidential? 
You have the right to confidentiality regarding the privacy of your medical information 
(personal details, results of physical examinations, investigations, and your medical history). 

By signing this document, you will be allowing the research team investigators, other study 
personnel, sponsors, institutional ethics committee to view your data, if required. 
 
26. What will be the treatment schedule(s)? 
If you participate in the study you will be given Vitmain D supplementation in addition to 
levocetrizine for 12 weeks. Thereafter supplementation will be stopped and only 
antihistaminics will be continued for the disease control.  
 
27. What compensation and/or treatment(s) are available to the Participant in the event 
of a trial-related injury? 
No compensation will be awarded however in the eventuality of any trial related injury 
(which is unlikely) you will be given treatment at PGIMER at no additional costs.  
 
28. Whom to contact for trial related queries and what are the rights of Partcipants in 
the event of any injury?  
You can contact the Prinicipal investigator(Dr M.Sendhil Kumaran) in the event of any 
injury. 
29. Are the participants paid to take part in this study? 
No payments will be given for participation in the study 
30. What are your responsibilities during participation in the study?  
 You will be required to come for the investigations and follow up as per treatment 
schedule. You will be called for 6 weekly follow up till completion of trial (18 weeks) 
and therafter as per your regular clinic scheduled visits 
 
31. Participation is voluntary, that the Participant can withdraw from the  study at any time 
and that refusal to participate will not involve any penalty or loss of benefits to which the 
Participant is otherwise entitled. 
 
32. Participant or Participant's representative will be notified in a timely manner if significant 
new findings develop during the course of the research which may affect the Participant's 
willingness to continue participation will be provided. 
 
33. If the participant is unable to come for follow up then his/her participation may be 
terminated by the Investigator without the Participant's consent.  
 
34. There will be no additional costs to the Participant that may result from participation in 
the study. 
 
 
35. Approximate number of Participants enrolled in the study- 150 
 
36. Any other pertinent information- No 
 

Contact persons:  
For further information / questions, you can contact us at the following address: 
 
Principal Investigator:  
Dr. M. Sendhil Kumaran 
Associate Professor 
Dept. of Dermatology, Venereology & Leprology 
Tel: 
Co-Investigator 
Prof. Dr. Davinder  Prasad 
Head of Department, Dept. of Dermatology, Venereology & Leprology 
 
 
Contact person(s): 
Dr. M.Sendhil Kumaran 
Associate Professor 
Dept. of Dermatology, Venereology & Leprology 
Email: drsen_2000@yahoo.co.in 
Tel: 8872004023 
 
In case of conflicts, you can contact the chairperson (convener) of our institutional ethics 
committee at the following address: 
Convener/Chairperson, Institutional Ethics Committee 
PGIMER, Chandigarh 
Telephone: ................ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Participant Information Sheet (PIS) for controls 
 
PROTOCOL NO: 
SPONSOR: 
PRINCIPAL INVESTIGATOR: Dr. M.Sendhil Kumaran 
Name of Participant:  
Title:  
1. You are invited to take part in this research study. The information in this document is 
meant to help you decide whether or not to take part. Please feel free to ask if you have 
any queries or concerns. 
 
2. What is your expected duration of the participation? 
Your participation in this study will last for a total of 18 weeks 
 
3. What procedures will be followed during this study? 
You will have to undergo Blood sample for biochemistry (S. Vit D, PTH, Ca, PO4,ALP) 
at baseline 
 
4. What are the risks and discomforts to you? 
The clinical examination, investigations to be done are safe and standard. Taking blood 
sample for biochemical analysis may cause slight pain but is routinely done  
 
5. What benefits are expected from this research? 
  This study will help us in Vitamin D deficiency in patients of chronic urticaria and factors 
associated with it. It will also help in finding out if vitamin D supplementation improves 
urticaria control in patients. It will also help in assessing if vitamin D deficiency is more 
prevalent in urticaria patients over normal controls 
 
6. What are the alternatives available to you? 
You will only be given vitamin D supplemtation if your vitamin D level is low 
(<30ng/ml) and rest care will the same as other patients. Antihistamincs will be given to 
you for the urticaria disease control 
 
7. Are the data/records of the participant kept confidential? 
You have the right to confidentiality regarding the privacy of your medical information 
(personal details, results of physical examinations, investigations, and your medical history). 
By signing this document, you will be allowing the research team investigators, other study 
personnel, sponsors, institutional ethics committee to view your data, if required. 
 
8. What will be the treatment schedule(s)? 
If you participate in the study you will be given Vitmain D supplementation in addition to 
treatment for your primary disease if found deficient .  
9. What compensation and/or treatment(s) are available to the Participant in the event 
of a trial-related injury? 
No compensation will be awarded however in the eventuality of any trial related injury 
(which is unlikely) you will be given treatment at PGIMER at no additional costs.  

 
10. Whom to contact for trial related queries and what are the rights of Partcipants in 
the event of any injury?  
You can contact the Prinicipal investigator(Dr M.Sendhil Kumaran) in the event of any 
injury. 
11. Are the participants paid to take part in this study? 
No payments will be given for participation in the study 
12. What are your responsibilities during participation in the study?  
 You will be required to come for the investigations and follow up as per your disease 
treatment schedule. No additional follow ups visits.  
 
13. Participation is voluntary, that the Participant can withdraw from the study at any time 
and that refusal to participate will not involve any penalty or loss of benefits to which the 
Participant is otherwise entitled. 
 
14. Participant or Participant's representative will be notified in a timely manner if significant 
new findings develop during the course of the research which may affect the Participant's 
willingness to continue participation will be provided. 
 
15. If the participant is unable to come for follow up then his/her participation may be 
terminated by the Investigator without the Participant's consent.  
 
16. There will be no additional costs to the Participant that may result from participation in 
the study. 
 
 
17. Approximate number of Participants enrolled in the study- 150 
 
18. Any other pertinent information- No 
 
Contact persons:  
For further information / questions, you can contact us at the following address: 
 
Principal Investigator:  
Dr. M. Sendhil Kumaran 
Associate Professor 
Dept. of Dermatology, Venereology & Leprology 
Tel: 
Co-Investigator 
Prof. Dr. Davinder  Prasad 
Head of Department, Dept. of Dermatology, Venereology & Leprology 
Contact person(s): 
Dr. M.Sendhil Kumaran 

Associate Professor 
Dept. of Dermatology, Venereology & Leprology 
Email: drsen_2000@yahoo.co.in 
Tel: 8872004023 
 
In case of conflicts, you can contact the chairperson (convener) of our institutional ethics 
committee at the following address: 
Convener/Chairperson, Institutional Ethics Committee 
PGIMER, Chandigarh 
Telephone: ................ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Informed Consent Form (ICF) for cases and controls  
 
 
 
 
Study Title:  A randomized controlled trial to evaluate the effect of Vitamin D 
supplementation in patients with  Chronic Urticaria 
Study Number (if any): 
Subject’s Initials: _______________ 
Subject’s Name:_______________ 
Date of Birth / Age: _________________ 
 
 
Participant's 
initial  
 
 
6. I confirm that I have read and understood the information sheet dated _ _ _ _  
for the above study and have had the opportunity to ask questions. 
 
 
7. I understand that my participation in the study is voluntary and that I am 
free to withdraw at any time, without giving any reason, without my      
medical care or legal rights being affected.  
 
8.   I understand that the Sponsor of the clinical trial, others working on the      
Sponsor’s behalf, the Ethics Committee and the regulatory authorities          
will not need my permission to look at my health records both in respect        
of the current study and any further research that may be conducted in          
relation to it, even if I withdraw from the trial. I agree to this access.         
However, I understand that my identity will not be revealed in any          
information released to third parties or published. 
 
9. I agree not to restrict the use of any data or results that arise from this     
study provided such a use is only for scientific purpose(s)  
 
10. I agree to take part in the above study  
 
 
Signature (or Thumb impression) of the Subject/Legally Acceptable 
Representative:_____________ 
Date: _____/_____/______ 
Signatory’s Name: ________________________________________ 
Signature of the Investigator: ____________________________               
Date:_____/_____/______ 
Study Investigator’s Name: ___________________________________