Tissue and Serum Level of NLRP1, NLRP3 and Il-18 in Early Stages of mf Patients

Study Overview
=================
Brief Summary
-----------------
To compare tissue and serum level of NLRP1, NLRP3 inflammasomes and Interleukin (IL)-18 in mycosis fungoids patients and normal controls. To compare tissue and serum level of NLRP1, NLRP3 inflammasomes and Interleukin (IL)-18 in mycosis fungoids patients before and after different treatment modalities.

Detailed Description
-----------------
Thirty patients with early stage mycosis fungoids and thirty normal healthy controls will be recruited. An informed written consent will be obtained from all patients and controls. Data collection Demographic data Each patient will be subjected to detailed history taking as regards age, sex, residence, marital status, smoking, special habits of medical importance, duration of the disease, associated diseases, previous therapy and family history. Evaluation of the clinical response The patients will be photographed and evaluated at baseline and at the end of treatment . Clinical scoring of five mycosis fungoids skin lesions will be done using Composite assessment of index lesion severity (CAILS) (Oslen et al., 2011). Clinical scoring of whole body affection will be done using Modified Severity Weighted Assessment tool (MSWAT) (Oslen et al., 2011). Assessment of response of mycosis fungoids patients to our treatment modalities will be done using Objective response rate (ORR) (Oslen et al., 2011). Treatment (therapeutic intervention): Thirty new patients with early stage mycosis fungoids will be allocated to proper treatment modality that differ according to the patient's clinical state following kasralainy phototherapy unit protocol End of the study will be defined as achieving clinically near complete clearance of the lesion from which a tissue biopsy will be taken or a maximum of 48 sessions of treatment. Biochemical assessment and pathological assessment (Diagnostic intervention) : Two lesional skin 4 mm punch biopsies will be taken from same lesion in all thirty patients and once from all thirty normal healthy controls. Three milliliter serum samples will be taken from all thirty patient before and after treatment and once from all thirty healthy controls. one skin biopsy and serum samples before treatment will be subjected to biochemical assessment for measurement of NLRP1, NLRP3 inflammasomes and Interleukin (IL)-18 by ELISA (Enzyme linked immunosorbent assay) technique. The other skin biopsy will be used for pathological assessment. The same process will be repeated after treatment for patients only to assess the percent change in all parameters and in lymphocytic infiltration . Fate of tissue and serum samples Tissue samples used for biochemical assessment will be completely crushed to extract protein for ELISA, any residual biological tissue will be safely discarded in the incinerator. Tissue samples used for pathological assessment will be put on paraffin blocks then on slides that will be kept in our department. Serum samples will be collected in special containers to be sent to the official site in the hospital to get rid of them. Intervention: Diagnostic intervention : biochemical assessment for measurement of NLRP1, NLRP3 inflammasomes and Interleukin (IL)-18 by ELISA (Enzyme linked immunosorbent assay) technique in tissue and serum samples of all thirty patients and healthy controls. Therapeutic intervention : Thirty new patients with early stage mycosis fungoids will be allocated to proper treatment modality that differ according to the patient's clinical state following kasralainy phototherapy unit protocol

Official Title
-----------------
Assessment of the Tissue and Serum Level of NLRP1, NLRP3 Inflammasomes and Interleukin-18 in Early Stages of Mycosis Fungoids Patients Before and After Different Treatment Modalities: Controlled Clinical Trial.

Conditions
-----------------
Early Disease Onset

Intervention / Treatment
-----------------
* Device: Puva (psoralin and uva )


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: New patients with early stages of mycosis fungoids (patch and plaque stage). Both genders Age group ≥ 18 years old. Exclusion Criteria: Patients with late stages mycosis fungoids(Tumor stage). Patients with absolute contraindication to phototherapy (e.g. any other skin cancers or photosensitivity); or to psoralen (e.g. liver disease). Subjects with history of solid or hematological malignancy as leukemia. Patients with autoimmune disease (e.g. SLE). Patients who received treatment of mycosis fungoids for the past one month. Pregnant and lactating females.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Thirty new patients with early stage mycosis fungoids will be allocated to proper treatment modality that differ according to the patient's clinical state following kasralainy phototherapy unit protocol
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 14 early mycosis fungoids patients<br>Puva (psoralin and uva) Measure nlrp1 and nlrp3 and il18 | Device: Puva (psoralin and uva )<br>* Intervention will be given for 48 sessions or till coplete resolution of biopsied plaque<br>* Other names: Retinoids;|
| Active Comparator: 8 mycosis fungoids patients<br>Puva (psoralin and uva) and methotrexate Measure nlrp1 and nlrp3 and il18 | Device: Puva (psoralin and uva )<br>* Intervention will be given for 48 sessions or till coplete resolution of biopsied plaque<br>* Other names: Retinoids;|
| Active Comparator: Eight mycosis fungoids patients<br>Puva (psoralin and uva)and retinoids (acetritin) Measure nlrp1 and nlrp3 and il18 | Device: Puva (psoralin and uva )<br>* Intervention will be given for 48 sessions or till coplete resolution of biopsied plaque<br>* Other names: Retinoids;|
| No Intervention: Controls<br>Measure nlrp1 and nlrp3 and il18 | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare tissue and serum level of NLRP1, NLRP3 inflammasomes and Interleukin (IL)-18 in mycosis fungoids patients and normal controls. | Diagnostic | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare tissue and serum level of NLRP1, NLRP3 inflammasomes and Interleukin (IL)-18 in mycosis fungoids patients before and after different treatment modalities. | Intervention of 48 sessions of puva alone or in addition to mtx or retinoids | 4 months | 
| Correlating tissue and serum level of NLRP1, NLRP3 inflammasomes and Interleukin (IL)-18 in mycosis fungoids patients with patient's age, sex, duration of disease, extent of disease. | Observational | 4 months |