Proforma to be submitted to the JIPMER Institute Ethics Sub-Committee (Human Studies) for MD/MS/DM/M.Ch/Ph.

D/MSc Students (for Thesis or Dissertation) 1. Title Of The Project : Therapeutic efficacy of intralesional steroids with carbon dioxide laser versus with cryotherapy in treatment of keloids: a randomised controlled trial. 2. Name and department/address of the investigator: Dr. Biswanath Behera Junior resident, Dept. of Dermatology and STD JIPMER, Puducherry-6 3. Name of Faculty with designation & department: Guide: Dr. Rashmi Kumari Assistant Professor, Dept. of Dermatology and STD, JIPMER, Puducherry-6 Co-Guide Dr. D.M Thappa Professor and Head, Dept. of Dermatology and STD, JIPMER, Puducherry-6 .

4. Date of approval by JIPMER Research Council: 14.10.2011

5. Sources of funding

: NA

6. Objectives of the study: a. To compare the therapeutic efficacy of combination of carbon dioxide laser followed by intralesional triamcinolone acetonide versus cryotherapy followed by intralesional triamcinolone acetonide in treatment of keloids. b.To study the recurrence rate following treatment with these two different combination therapies. 7. Justification for the conduct of the study: Previous studies have shown that combination therapy of intralesional steroid with both carbon dioxide laser and cryotherapy have higher efficacy and reduced recurrence rate in comparison to carbon dioxide laser or cryotherapy alone, in treatment of keloids. The duration of treatment is reduced with improvement of quality of life. The side effects associated with combination therapy is also minimal as the number of intralesional steroids to be given for each keloid are reduced. However no study has compared the efficacy of these two modalities of treatment. So we are doing the study to compare the therapeutic efficacy and side effects associated with these two modalities. 8. Reasearch Plan/ Study Design With Inclusion And Exclusion Criteria: a) Whether the study involves animals, humans or both : Humans only. b) Type of study (Study design) c) Number of groups to be studied d) Sample size 1. Inclusion criteria study if they are a. Of size less than 5 cm in any dimension. b. Multiple keloids less than 5 in numbers : : Randomized controlled study : Two : 40

All the keloids irrespective of gender, site of involvement, duration of lesion will be included in the

2. Exclusion criteria

a. Age less than 12 years and greater than 60 years. b. Pregnant and lactating women. c. Keloids with concomitant infection. d. Coexisting inflammation in adjacent skin secondary to dermatological diseases (such as psoriasis, lichen planus, eczemas, etc.) e. Patients with unrealistic expectations or psychiatric illnesses. f. Preexisting bleeding disorder, renal or hepatic diseases e) Parameters to be studied Clinical variables: 1. Keloid measurement: height, length and width with dial calipers. 2. Time for healing following the procedure in 2 groups in days. 3. Patients self assessment (subjective) response and POSAS score (patient and observer scar assessment score).
4.

Demographic variables: age, sex, occupation, family history.

Observers assessment by photographic analysis and VSS (Vancouver scar scale) by an independent blinded observer.

5. Side effects of each modality. 9. Laboratory parameters: Haemoglobin levels, complete blood count, liver and renal function tests. 10. Brief procedure: Participants will be randomly allocated into two groups, group1 and group2 by simple randomization. On day 1, keloids in group1 will be ablated using carbon dioxide laser and keloids in group2 cryotherapy will be done. In both the groups injection lignocaine(2%) will be given prior to procedure and intralesoinal triamcinolone acetonide will be given after the procedure. Participants will be prescribed cap. Cloxacillin 500mg qid for 5 days to prevent any infections, tab chlorpheniramine maleate 4mg bd for itching and tab paracetamol 500 mg for pain at site of lesion. Participants will be advised to keep the area clean and dry. At the end of 1st week participants in both groups will be reviewed to find out any side effects of the treatment, if any will be treated with standard guidelines. At monthly intervals intralesional triamcinolone acetonide will be given at the

elevated margin in both groups. At the end of 3rd month and 6th month both groups will be reviewed for therapeutic response. At the end of 1st year both group will be evaluated for any recurrence of keloid. At day 1, end of 3rd month, 6th month and 1st year standardized photographs and various measurements according to protocol will be done by a independent blinded observer.

9. Permission from Drug Controller General of India (DCGI) : No

10. Ethical issues involved in the study : Minimal Risk a) Written informed consent will be taken from all the patients before the start of the study. b) The study shall be conducted in accordance with the Declaration of Helsinki.

11. Do you need exemption from obtaining Informed Consent from study subjects?

No

12. Whether Consent forms part 1 and 2 in English and in local language are enclosed? Yes

13. Conflict of interest for any other investigator

: No

We, the undersigned, have read and understood this protocol and hereby agree to conduct the study in accordance with this protocol and to comply with all requirements of the ICMR guidelines (2006)

SIGNATURE OF THE CANDIDATE

SIGNATURE OF THE GUIDE Assistant Proffesor Dept. of Dermatology and STD, JIPMER, Puducherry-6)

SIGNATURE OF THE CO-GUIDE: Dr. D.M Thappa Professor and Head, Dept. of Dermatology and STD, JIPMER, Puducherry-6

SIGNATURE OF THE HEAD OF DEPARTMENT: Dr. D.M Thappa Professor and Head, Dept. of Dermatology and STD, JIPMER, Puducherry-6

CONSENT FORM PART 1 of 2 INFORMATION FOR PARTICIPANTS

1. Title of the project: Therapeutic efficacy of intralesional steroids with carbon dioxide laser versus with cryotherapy in treatment of keloids: a randomized controlled trial. 2. Name of investigator/guide: Dr. Rashmi Kumari Assistant Professor Dept. of Dermatology and STD JIPMER, Puducherry-6 3. Purpose of project or study: Keloids are benign overgrowth of tissue that usually occurs following trauma like ear piercing, burn, cut on skin, injection, abscess, acne etc. Rarely it can occur without any trauma. Patients usually complain pain, itch and cosmetic disfigurement. Keloids are routinely treated with intralesional steroids, carbon dioxide laser and cryotherapy. In intralesional procedure we give steroid injections at the margin of the growth at monthly interval. It reduces the pain, itch and size of lesion but patient has to come for long time for repeated injections and the growth may reappear again at same site. In carbon dioxide laser we give current light to the keloid to destroy it at one time but here growth reappears again at the same site. In cryotherapy we freeze the growth by using ice from an instrument, which destroys the growth but here also growth reappears again. But we have seen that if we destroy the growth using either carbon dioxide laser or cryotherapy and give injection of steroid monthly then growth disappears in less time and it rarely reappears again. This combination treatment reduces patients suffering and saves their valuable time. In this study we are combining intralesional steroid with either carbon dioxide laser or cryotherapy to reduce your suffering in lesser time and improve your cosmesis. 4. Procedure/ methods of study: If you have less than 5 keloids and their maximum size is less than 5 cms than you can be part of this study. There are two study groups; group 1will be given carbon dioxide laser followed by injections of steroid and

group 2 will be given cryotherapy followed by injections of steroids. I will include you in one of the study groups since cure rate with both treatment modalities is almost same. On 1st day injection will be given to block your all your sensation at the site of lesion, then we will use laser light or ice using cryotherapy machine to the growth(keloid) following which injection of steroid will be given. You will be provided with tablets which will reduce the chance of infection, pain, itching and promote faster healing. You have to come at the end of 1st week to see for appropriate healing of the wound and side effects, if any will be treated appropriately. After that you will be given monthly injections of steroids for 3 months into the growth. At the end of 3rd month we will see the improvement of lesion by taking measurements of the keloid. If you have improved completely by 3 months then you would be asked to come and see the doctor again at the end of 6th month. If you have not improved significantly, we will continue giving the injections at monthly intervals till the desired effect of complete flattening of your keloid. Lastly you have to come at the end of 1st year to see if after completely subsidence of the lesion if there is any reappearance of the growth. On day 1 and after end of 3rd month, 6th month and 1st year I will also take photograph, will measure the keloid and ask you questions to evaluate how much improvement has occurred after this treatment. You will also be required to come back to hospital as intimated to you at regular intervals for 1 year the period for which you will be under treatment evaluation. 5. Expected duration of subject participation: One year 6. The benefits to be expected from the research to the participant or to others and post trial responsibilities of the investigator: Participants can avail faster relief from pain, itch and cosmetic disfigurement with lesser chance of reappearance of the benign growth than if they receive any modality of treatment alone. If there is any significant difference in the outcome of the two groups we will inform the patients accordingly. This information will be useful to the doctors in planning future treatment for keloid patients. Post trial we would continue to give you the steroid injection into the growth if you desire so, or allow you to choose from other alternatives for treatment. If you feel satisfied with this treatment protocol or the alternative protocol in the event of recurrence of the keloid we would provide you with the same.

7. Any risks expected from the study to the participant: The risk associated with the study is minimal. Injection of steroid is associated with pain at injection site, thinning of skin, change in colour of skin. Carbon dioxide laser may cause ulceration, pain for 1 week till the ulceration heals. Cryotherapy may cause blistering, pain and ulceration. Chance of change in colour of the skin after the treatment is there but the therapy is more likely to make the growth less obvious by flattening it. You can also avoid the skin becoming darker by avoiding excessive sun exposure immediately after procedure for 2 weeks. Any side effect like pain and ulceration are temporary and will be treated appropriately. 8. Maintenance of confidentiality of records: All your study records will be kept confidential. Your personal identity will not be revealed in any publication or release of the results. Study records will also be kept for further analysis and follow-up, if needed. 9. Provision of free treatment for research related injury: Risk of injury related to the treatment includes ulceration, pain and secondary infection. You will be treated freely for the same and we can manage all the complications which may arise related to this treatment protocol. 10. Compensation of the participants for disability or death resulting from such injury: Yes, although the chance of any serious injury is very little. In case of such an event compensation will be provided. 11. Freedom to withdraw from the study at any time during the study period without the loss of benefits that the participant would otherwise be entitled: You are free to withdraw from the study at any time during study. It will not affect your further treatment and regular alternative treatment as you may desire will be given to you. 12. Possible current and future uses of the biological material and of data to be generated from the research and if the material is likely to be used for secondary purpose or would be shared with others, this should be mentioned: Data from this study will be kept confidential with the investigators and the results of this study will be used for scholarly purposes only. The results may be presented in educational settings like conferences or published in a professional journal but will not reveal your identity in any manner. Sharing of such valuable information may help doctors to plan better therapy for keloids in future.

For any study related queries, you are free to contact,

Name of the contact person with official address and phone number:

Dr. Biswanath Behera Junior Resident Department of Dermatology and STD JIPMER, Puducherry - 605006. Phone No. 9626603810

Place: Puducherry Signature of investigator

Date: Witness:

CONSENT FORM

PART 2 of 2- Participant consent form

Participants name:

Address:

Title of the project: A COMPARISON OF THERAPEUTIC EFFICACY OF INTRALESIONAL STEROIDS IN COMBINATION WITH CARBON DIOXIDE LASER VERSUS IN COMBINATION WITH CRYOTHERAPY IN TREATMENT OF KELOIDS.

The details of the study have been provided to me in writing and explained to me in my own language. I confirm that I have understood the above study and had the opportunity to ask questions. 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. 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). I also received a copy of the Consent Form 1 of 2 giving the Information for participants of the study. I fully consent to participate in the above study. Signature of the participant: ______________________ Date: _____________

Signature of the witness: ________________________ Date: _____________