HIV/AIDS clinical trails at LTMMC & General Hospital, Sion, Mumbai

Project Application for IRB & Ethics Committee

1. Project Title: Efficacy Trails of RECEPTOL, a pure natural product on 50 AIDS Patients based on Indian FDA & ICMR recommended protocols

2. Principal Investigator:

1. Dr. N.K. Hase, MD Professor & Head: Dept. of Medicine
2. Director General: National AIDS Control Organization

3. Investigators:

1. Dr. Alka Gogate, Project Director, Mumbai AIDS Society
2. Dr. G.C. Rajadhyaksha, Assoc. Prof. of Medicine
3. Dr. Mayank Shah, President, Helium Hospital
4. Dr. Neelam Redkar, Head, HIV Unit
5. Dr. Sandhya Saharan, OBGY Specialist
6. Dr. Asha Shah, Hematologist
7. Ms. Nirzari Parikh, MS (Cambridge UK): Chief Technical officer
8. Dr. Suresh Advani, Chief Oncologist (Consultant of Study)

4. Introduction and background of the Project

4.1 Definition of the Study with Brief Introduction:

This study will test the safety and effectiveness of RECEPTOL® Liquid for treating people infected with HIV. Cell fusion of HIV particles with human white blood cells, particularly CD4 cells with the aid of glycoprotein epitopes on the viral wall. It is believed that the informational proteins in RECEPTOL® are active in mitigating cell fusion by impacting the HIV glycoprotein' ability to attach and fuse with CD4 cells.

4.2 Aims & Objectives of the project:

This study will determine what effect of oral administration of RECEPTOL® Liquid has on viral load, CD4, CD8 cells and HIV/AIDS symptoms in the patients.

4.2 Place of Study: LTMMC & General Hospital, Sion, Mumbai 400 022

4.2 Duration of the Study: 12 Weeks

5. Study Description

5.1 Design:

Phase III Efficacy Study for Receptol is designed for HIV-positive patients between the ages of 18 and 60. Candidates will have a medical history, physical examination, blood and urine tests, and chest X-ray, and possibly other tests as determined by the clinician in guidance with the principal investigator.

Participants will receive RECEPTOL® Liquid in pump spray form. Patients will be taught to self-administer RECEPTOL®. Frequency of administration is 4 times per day. Each administration will consist of three (3) spays directly on the buchal mucosa (inner cheek). Each pump of the spay delivers 0.7ml of RECEPTOL®. This study will continue for 12 weeks.

Participants will be evaluated in the clinic once a week through the first 4 weeks of therapy, then every 2 weeks for the remaining 8 weeks of the initial study. They will be asked about side effects of treatment and may have a physical examination. Blood tests to measure CD4 cells and HIV viral load will be done at each evaluation.

Further Study Details: This study will involve a single arm, open label, 12-week study in 50 subjects to determine increase of CD4 and CD8 counts associated with RECEPTOL ® supplementation in subjects with HIV / AIDS.

This is a study to determine the efficacy of RECEPTOL ® given over twelve (12) weeks. The study is designed to investigate potential for RECEPTOL® therapy to reduce viral load and increase CD4 levels. As mentioned the primary endpoints of the study include effect of this therapy on markers of HIV disease including the HIV-viral load and CD4 cell counts along with general well being of the patients.

5.2 Methodology: Sample size & Sampling Method

Total Enrollment: 50

Eligibility: Genders Eligible for Study: Both Male & Female Subjects

5.3: Definition of subject/material to be used:

Criteria

a) INCLUSION CRITERIA:

• Subjects should be between 18 and 60 years of age.
• Documentation of HIV infection by any licensed ELISA test.
• Subjects must have CD4 count greater than 100 cells/mm(3)
• Subjects will have measurable HIV viral load.
• Subjects must have the ability to give informed consent.
• Willingness to give informed consent.
• Willingness to be able to make follow up visits once per week for the first four weeks and once every other weed for eight weeks

b) EXCLUSION CRITERIA

• Pregnant or nursing women, women of childbearing potential not using an adequate method of birth control
• Subjects with kidney disease or serum creatinine greater than 1.5 mg/dL
• A history of hepatic cirrhosis.
• Congestive heart failure.
• Evidence of a severe or life-threatening infection.
• Treatment within the last 2 months with systemic gluco-corticoid steroids
• Any medical condition that, in the opinion of the Principal Investigator or Study
• Chairperson would preclude the inclusion of a patient onto this study.
• Active systemic infections other than hepatitis C and HIV.
• Hemochromatosis, autoimmune hepatitis (ANA greater than 160) except history of drug-associated hepatitis with discontinuation of the causative agent.
• Liver disease caused by reasons other than hepatitis C like HBV, HDV, Wilson'sHepatic mass suggestive of hepatocellular carcinoma.
• Current alcohol or substance abuse that potentially could interfere with patientcompliance.
• Any systemic illness that will make it unlikely that the subject will be able toreturn to LTMMC, Sion Hospital, Mumbai Clinical Research for the required study visits.
• Organ transplant recipient.
• Preexisting uncontrolled seizure disorder.
• No subjects using long term systemic corticosteroids, immuno-suppressive, or

5.4 Parameters to be studied at the initiation of the study

Blood tests to measure CD4 cells and HIV viral load will be done along with other examinations as per the inclusion criteria for the patients given above.

5.5 Parameters to be studied at follow up along with duration of follow up

Blood tests to measure CD4 cells and HIV viral load will be done as per the detailed Methodology along with study protocols given above for a duration of 12 weeks.

5.6 Organisation of work elements: Names of the Milestones

PROJECTED SCHEDULE PHASES:

Phase I :

Subject recruiting, Document drafting

Hospital Ethics Committee Clearance & Duly Signed Consent Forms by the Patients

Phase II (4weeks-Subjects to visit clinic once per week):

Week 1

• Subjects will deliver medical case history records to LTMMC, Sion Hospital, Mumbai to initiate the Case Report Form
• Explanation of study, study is an Open Study
• Informed Consent Form executed .
• Study subject may complete Quality of Life Survey
• Initial Physical Examination including Vital Signs, Height, Weight, temperature and will assess the Skin, Heart, Lungs, Neuro., extremities & Chest X-rays
• Initial blood work to establish baselines (CD4, CD8, HIV Viral Load)
• Study subjects directed in self administration of RECEPTOL®
• Initial administration or RECEPTOL® done in clinic
• Study subjects to self-administer RECEPTOL® as directed three (3) sprays to the buchal

mucosa every four hours during waking hours

Week 2 (Subjects using RECEPTOL® one week)

Study subjects return to clinic for blood work and evaluation (CD4,CD8 Count)

Week 3 (Subjects using RECEPTOL® two weeks)

Study subjects return to clinic for blood work and evaluation (CD4,CD8 Count)

Week 4 (Subjects using RECEPTOL® three weeks)

Study subjects return to clinic for blood work and evaluation (CD4, CD8, HIV Viral Load)

Week 5 (Subjects using RECEPTOL® four weeks)

Study subjects return to clinic for blood work and evaluation (CD4, CD8, HIV Viral Load)

Subjects complete second Quality of Life Survey

Phase III (8 weeks-Subjects to visit clinic every other week, once in 15 days):

Week 7 (Subjects have been using RECEPTOL® 6 weeks)

Study subjects return to clinic for blood work and evaluation (CD4, CD8, HIV Viral Load)

Week 9 (Subjects have been using RECEPTOL® 8 weeks)

Study subjects return to clinic for blood work and evaluation (CD4, CD8, HIV Viral Load)

Week 11 (Subjects have been using RECEPTOL® 10 weeks)

Study subjects return to clinic for blood work and evaluation (CD4, CD8, HIV Viral Load)

Week 13 (Subjects have been using RECEPTOL® 12 weeks)

Study subjects return to clinic for blood work and evaluation (CD4, CD8, HIV Viral Load)

Subjects complete final Quality of Life Survey

Phase IV

Data analysis and report generation

Study results presented to ICMR & DCGI

Starting Date: February 7, 2005

Expected date of Completion: Approx. 4 months from the starting date

5. 7 Staff to be appointed (if any)

6. Work Already Done in the field

RECEPTOL^®- demonstrated in-field and clinical use with more that 2000 HIV infants, children and adults in twelve countries. There have been no known exceptions to the ability to affect the progression of many chronic degenerative diseases for which it has been used. In many cases, the formula has induced what appears to be complete and lasting cellular recovery.

RECEPTOL^® has shown to be effective in treating many different diseases and condition. However, it is prudent to focus attention on a few well-known diseases. Initially, Rheumatoid Arthritis was the selected disease to put under the microscope. The success of treating this autoimmune condition led to the selection of a high profile disease - HIV.

Receptol treatment of - HIV: African Trial Results Report

Phase 1 - HIV trial

Population: 12 cohorts, term: 30 days and moderate control of product use. The patients in this study should be presumed to have had previous exposure to chemo-therapy (AZT). Neither the doctor nor patients were made aware of the positive potential of this product. A balanced diet of carbohydrates, proteins, fats, vitamins and minerals were administered in conjunction with the treatment.

Results

Weight Gain

• 10 out of 12 gained weight during the thirty-day trial period.
• Of the 10 that gained weight, 7 (70%) gained an average of 6 lbs
• 5 patients gained 6 lbs in one month, while 2 others 5.5 and 6.6 lbs respectively
• the highest weight gain of 12 lbs was recorded for a patient who had been HIV positive since 1986 (10 years)

Number of Patients	Number of lbs Gained
1	+12.0
1	+6.5
5	+6.0
1	+5.5
2	+2.0
1	+0.0
1	-0.4

Diarrhea

• 8 out of 10 patients had various levels of diarrhea (mild, moderate or severe) at the beginning of the trial period
• Of the 8, 5 patients (62%) went from varying levels of diarrhea severity to NO diarrhea.
• The 1 patient without weight gain experienced total elimination of severe chronic diarrhea and a return to solid stool formation.

Nausea

• 8 out of 12 patients had various levels of nausea at the beginning of the trial period.
• Of the 8, 5 patients (62%) went from varying levels of severity of nausea to No nausea.
• Of the remaining 3 patients, with some degree of nausea, 2 experienced a reduction in the severity of their symptoms.
• 9 out of 10 patients, who reported fatigue symptoms at the beginning of the trial, experienced an increase in their level of energy.
• 3 out of 10 experienced a significant increase in energy, from initial varying levels of fatigue to NO fatigue.

Cough

• 4 out of 12 had either a mild to moderate cough at the beginning of the trial
• 2 of the 4 reported NO cough at the end of the trail period.
• Of the remaining 2 individuals, 1 reported a reduction in the severity of his cough.

Symptoms Assessment Score

• All 12 patients experienced an improvement in their overall symptoms assessment score.
• The average reduction approached 2/3 (63%) - Dr Brandt.

Phase 2 - HIV trial

Phase 2 of the study on HIV was completed in Nairobi, Kenya.

Objectives: To demonstrate, under clinical conditions, the safety and efficacy of info protein supplementation in patients known to have advanced disease (HIV/AIDS), compromised immune resources and limited access to conventional treatment.

Population: 30 cohorts, term: 30 days and moderate control of product use.

Considerations: Unless otherwise noted, the patients in this study should be presumed to have no previous exposure to chemotherapy (AZT). Some patients could not refrigerate the product after opening, therefore exposing it to the denaturing effect of bacterial contamination.

The patients were not made aware of the positive potential of the product.

Results

• The product appeared to be free of side effects and generally well tolerated by the participants. Some signs, consistent with detoxification, were noted but resolved when the patients increased their water consumption.
• The product demonstrated significant value by reducing or resolving the symptoms of opportunistic infections most commonly associated with the dynamic of HIV/AIDS.
• Patients often experienced weight gains as part of an overall pattern of positive response.

Summary

Positive clinical results observed in the Nairobi patients.

Phase 3 - HIV trial

Phase III study on HIV Patients in Rwanda.

Objectives: To demonstrate, under clinical conditions, the safety and efficacy of info-protein supplementation in patients known to have advanced disease (HIV/AIDS). Cohorts were all symptomatic, ambulatory, compliant and native to anti-retroviral therapy.

Population: 60 cohorts, term: 365 days and moderate control of product use.

Considerations: All cohorts receive oral supplementation of RECEPTOL^® every 6 hours for a period of 365 days. Some patients could not refrigerate the product after opening, therefore exposing it to the denaturing effect of bacterial contamination.

The patients were not made aware of the positive potential of the product.

Results

• The product appeared to be free of side effects and generally well tolerated by the participants. Some signs, consistent with detoxification, were noted but resolved when the patients increased their water consumption.
• The product demonstrated significant value by reducing or resolving the symptoms of opportunistic infections most commonly associated with the dynamic of HIV/AIDS.
• Patients often experienced weight gains as part of an overall pattern of positive response.
• After 1 day of use there was a moderate level of relief of fever and diarrhea.
• After 14 days of use all patients experienced relief of skin lesions, mouth thrush, fever, diarrhea, tuberculosis.
• After 90 days of use all patients experienced relief of all symptoms.
• After 330 days all patients are still not experiencing any negative symptoms.

Discussion

In brief, the patients recovered very quickly but complain of INTENSE HUNGER AND THIRST. It is VITAL TO INTERVENE BY GIVING PROTEIN SUPPLIMENTATION to be able to observe the body reconstruction as most patients are very poor and have low protein intake. Generally speaking there is an excellent recovery for all patients that have been on the product but the EXTREME HUNGER is hindering the weight gain process. - Dr. Rusibira, Internal Medicine Specialist.

Summary

Positive clinical results are continually observed in the Rwanda patients even after 12 months of completion of trails.

7. References: Xerox copy attached.

8. Comments by Bio-Statistician: Drug Controller General of India on ICMR recommendation has already approved 50 AIDS patients trails for Receptol in India based on US FDA and NIH guidelines.