Efficacy and safety of Bacillus Calmette Guerin (BCG) vaccine and Purified protein derivative (PPD)in treatment of viral warts

Phase 4

Recruiting

Conditions: Multiple viral warts

Registration Number: CTRI/2014/12/005244

Lead Sponsor: Medical College Kolkata

Brief Summary: Viral wart is one of the most commonly known dermatological diseases, caused by human papilloma virus (HPV) which is notorious for its contagious nature. It can affect people of both sexes, no age group being spared. Usually these warts heal spontaneously, although that takes a long time. However, in certain instances healing does not occur spontaneously even after long periods of follow up. There are many modalities of therapy such as electocautery, chemicocautery, cryotherapy, and others, most of these take months and many of them being destructive may result in scarring and the recurrence rates after this therapy may be high. In such cases, the warts are said to be recalcitrant to treatment, and often such warts are multiple in number. Such recalcitrant, multiple viral warts are a cause of great concern to the patient and the treating dermatologist. The management of such warts is often frustrating, and they pose a great therapeutic challenge to the dermatologist, being non-responsive to conventional treatment.

Recently, to cope up with this challenge, dermatologists have come up with a plethora of newer, intuitive management strategies that are evolving with each passing day. Most of these newer strategies act by strengthening the immune system to combat the menace of warts; so they are rightly regarded as immunotherapy.

Recently, Tuberculin antigen and Bacillus-Chalmette-Guerin(BCG) vaccination have garnered the attention of the entire dermatological fraternity for the treatment of such resistant warts, as some studies have sparked interest in them. Initially BCG was introduced as a prophylactic agent against tuberculosis, but now itâ€™s also used in the treatment of malignant melanoma, transitional cell carcinoma of the bladder, alopecia areata and recurrent oral aphthosis. The proposed mechanism of its action is by the stimulation of macrophages, B and T lymphocytes, NK cells. TLR 7 may also play a role.

In the present study, we would like to access and compare the effectiveness of BCG vaccination and tuberculin antigen (purified protein derivative / PPD) for the treatment of multiple viral warts in an Indian setting, as such a study is lacking in our set-up. We would also take into account the safety and tolerability of these treatment regimens. As far as our knowledge, such a comparative study between two of the most promising newer therapies has not been published in any indexed journal till date.

The objectives of the study are to evaluate and compare the effectiveness of BCG vaccine and PPD derivative of tuberculin protein in the treatment of multiple viral warts and to assess and compare the safety and tolerability of the above mentioned treatment regime.

The patients would be included in the study as per the following inclusion and exclusion criteria.

INCLUSION CRITERIA

i.            Male or female patients between 18 and 65 years of age (both inclusive)

ii.            Multiple viral warts (number > 10)

iii.            Patients who give their informed consent

EXCLUSION CRITERIA

i.            Pregnant or lactating women

ii.            Any evidence of immunosuppression (egg HIV infection, Organ transplantation, long term steroid use etc.)

iii.            Any other systemic disease (egg liver, kidney disorder)

iv.            Patients not giving their informed consent

v.            Presence of mucosal wart(s)

This institution-based, randomized, prospective, double blind, parallel group, comparative trial will be carried out in the Department of Dermatology, Medical College and Hospital, Kolkata, a tertiary care centre in Eastern India.

Every patient will be given treatment for 3 months (either BCG or PPD according to randomization) at monthly intervals. They will be followed up for the next 3 months, total study duration of 6 months. The study will be complete after the last follow up of the last recruited patient.

We expect to study about 30 patients in each arm, a total of 60 patients.

**Study procedure:**

After obtaining written informed consent form each patient, screening will be done (1st visit). At screening, patientsâ€™ demographic details (age, sex, weight, and height) and detailed medical history (including history of hypersensitivity, other systemic diseases, concomitant medication and previous treatment) will be recorded. Physical examination will include localization and determining the number of warts. Blood will be collected for hematology, biochemical analysis (urea, creatinine, LFT). The schedule of each patient is given below:

1st visit Ã Screening visit (Informed consent obtained, Clinical and biochemical parameters noted)

2nd visit Ã ***Baseline visit*** (1st dose of injection given either 0.1 ml BCG or PPD tuberculin according to randomization)

3rd visit (after 1 month of baseline visit)Ã ***1st Follow up visit*** (2nd dose injection given, clinical parameters noted)

4th visit (after 1 month of 1st Follow up)Ã ***2nd Follow up visit*** (3rd dose injection given, clinical and biochemical parameters noted)

5th, 6th and 7th visit (after 1 month of 2nd, 3rd and 4th Follow up respectively)Ã ***3rd , 4th , 5th Follow up visit respectively*** (clinical parameters noted)

**Randomization and blinding:** Eligible patients will be randomized into either group A (BCG vaccine) or group B (PPD of tuberculin antigen) with allocation ratio 1:1 as per the randomization sequence (balanced unstratified randomization using Winpepi software ETCETERA version 2.32 which is a WINPEPI (PEPI-for-Windows) program) generated by an independent coordinator (IC). Allocation concealment will be done by sequentially numbered opaque sealed envelope (SNOSE) technique.

After thorough evaluation the investigator will refer patient to independent coordinator (IC) who will assign treatment to patients according to SNOSE and supply the medication to the treating physician who will be unaware of the randomization. The treating physician will inject the medicine and will take note of the clinical parameters. Both the investigator, the treating physician and the patients will be blind to treatment allocation.

The statistical analysis is will be performed by an individual who will be blinded to the treatment arms and would identify the treatment received by the patients in terms of code (group A or group B).

Route of administration of BCG/PPD:

Ã¼ Palmar, Plantar and facial warts Ã Intradermal injection on right arm (at deltoid muscle insertion)

Ã¼ Warts in other regions: Intralesional injection is given in the largest wart (candidate wart)

**Follow-up visits:**

All the patients will be rigorously followed up as per the schedule given above. At each follow up the following points will be enquired upon:

o   Any abscess formed at the site of injection, if formed, it would be examined and the largest diameter of induration would be measured in each visit; erythema would not taken into account.

o   If ulceration takes place, proper history will be taken regarding the evolution of the abscess.

o   If active discharge, pain are present suitable antimicrobials and analgesics will be prescribed for symptomatic relief.

o   Formation of any scar

o   Occurrence of any other adverse effect, if yes: it will be properly notified.

o   All the findings would be photographed and preserved for future reference.

**Process of administration of injection (the preparation of the medication will be done by the independent coordinator):**

**BCG:**

Freeze dried, powdered form of BCG vaccine is taken and diluted with 1 ml of normal saline, supplied with the vial of BCG vaccine.

After preparation, 0.1 ml of BCG vaccine is administered intralesionally or intrademally (as per criteria) with the help of an insulin syringe.

Each prepared vial is finished within 4 hours of opening, as per standard norms.

**PPD:**

0.1 ML of PPD (5 TU in 0.1 ml) is administered intradermally as per criteria stated above.

Detailed Description: Not available

Recruitment & Eligibility

Status: Open to Recruitment

Sex: All

Target Recruitment: 60

Inclusion Criteria

i.Male or female patients between 18 and 65 years of age (both inclusive) ii.Multiple viral warts (number > 10) iii.Patients who give their informed consent.

Exclusion Criteria

i.Pregnant or lactating women ii.Any evidence of immunosuppression (egg HIV infection, Organ transplantation, long term steroid use etc.) iii.Any other systemic disease (egg liver, kidney disorder) iv.Patients not giving their informed consent v.Presence of mucosal wart(s).

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Number of warts	Baseline, 1, 2, 3, 4, 5, 6th month. \| Every patient will be given treatment for 3 months (either BCG or PPD according to randomization) at monthly intervals. They will be followed up for the next 3 months, total study duration of 6 months.

Secondary Outcome Measures

Name	Time	Method
Serum for Liver Function Test, urea, creatinine, Hemoglobin, Total count, Differential Count, Erythrocyte Sedimentation Rate	Screening visit, 3rd month visit

Trial Locations

Locations (1): Medical College, Kolkata
🇮🇳
Kolkata, WEST BENGAL, India
Medical College, Kolkata
🇮🇳Kolkata, WEST BENGAL, India
Dr Nilay Kanti Das
Principal investigator
9433394148
drdasnilay@gmail.com