Clinical Trial Protocol

I. BACKGROUND

Pommer coined the term osteoporosis in 1885, which literally means increased porosity of bones. It is described as a systemic skeletal disease characterized by low bone mass and micro architectural detofiation of bone tissues with a consequent increase in bone fragility and susceptibility to fracture. The magnitude of the problem has not been fully understood and the incidence of osteoporosis is highly increased due to increased life span and greater awareness of the disease since 1980 (Rosen et al, 1997). In recent study the following observations were made.

1)    Osteoporosis’ occurs both in males and females in India.

2)    Nearly one out of five adults have osteoporosis in which prevalence is higher in women and in elderly.

3)    Osteoporotic fractures occur more commonly in Indian males than females.

4)    Osteoporotic fractures occur 10-20 years earlier in Indian men and women compared to west (Wali, T.P. etal)

5)    Prevalence of osteoporosis was slightly higher in females than males (19.4 vs 17.3%)

Certain factors like Genetic, personal life style factors like smoking, alcoholism lower intake of calcium, non-exposure to sunlight and certain diseases predispose this disease.

In Ayurveda under the heading "Asthi kshaya" many signs and symptoms described can closely be correlated with this clinical entity. This has also been treated with herbal and herbo minerals medicines since very remote past. Kukkutand Twak Bhasma (Egg shell bhasma), Shigru (Moringa olifera Lam.), Arjun (Terminalia arjuna (Roxb.) Wight & Arn.), Ashwagandha (Withania somnifera L.), Laksha (Laccifer lacca Kerr), Haritaki (Terminalia chebul Retz.), Dinka (Cestrum diurnum L.), Yawa (Amorphophalluys paeoniifolius (Decne.) Sivad.), Guduchi (Tinospora cordifolia Gulbel), Babbul twak(Vachellia nilotica subsp. indica (Benth.) Kyal. & Boatwr.) 

In modem medicine this disease is managed with, Hormone replacement therapy and also with calcium and Vitamin ’D’ which is considered as anti resorptive and stimulator of Bone turn over. But these drugs do have side effects like nausea, vomiting and diarrhea. In this contest the natural calcium, which is safe, less toxic, and does not have any side effect will be taken for study.

II.     AIM:

       To assess the therapeutic efficacy Sudhatatva’s Asthiposhak Vati in the treatment of osteoporosis.

III.   OBJECTIVES:

To evaluate the therapeutic efficacy of an Ayurvedic trial drug Asthiposhak tablets in the treatment of osteoporosis in comparison with standard control drug Calcium with Vitamin- D3.

IV.   CENTRE:

OPD of  Dr. D.Y.P. College of Ayurved and Research Center, Pimpri

V.     METHODS :

Groups:                                   Two-Trial group and Control group (30 cases in each group)

Group-I:                                  Trial group

Group-II:                                 Control group

Trial Design:                           Randomized Control Trial

Trial drug:                               Sudhatatva’s Asthiposhak Vati 500mg each twice a day

Control drug:                          Calcium tablets with Vit-D3 500mg twice a day

Duration of treatment:            12 Weeks

Period of Study:                      3 months

VI.    INCLUSION CRITERIA

1.      Age: Patients of both sexes above 45 years and up to 70 years.

2.      B.M.D. T. Score below — 1.5

The cases for carrying out BMD T Score will be screened with the following targeted patients:

3.      Post menopausal woman with early menopause (40 years and below) and familial prevalence.

4.      Patients with osteopenia or spinal deformities on spine-x-rays.

5.      Patients on long-term cortico steroids for more than six months

6.      Patients with history of osteoporosis related fractures.

VII. EXCLUSION CRITERIA

1.    Patients have history known cases of - Primary Hyper parathyroidsim,      Thyrotoxicosis, Addison’s disease, Cushing syndrome, Rheumatoid arthritis,   Malabsorption syndrome, Chronic liver diseases, Diabetes (Uncontrolled).

2.    Organ transplantation

3.    Chronic renal failure

4.    Prolonged immobilization

5.    Cases undergoing treatment for osteoporosis

6.    Cases undergoing treatment for any other serious illness.

VIII. ROUTINE EXAMINATION AND ASSESSMENT

Clinical assessment will be done at (0), at the end of 1^st, 2nd and every subsequent month till the completion of treatment (Form 2). The Lab investigations (Biochemical markers) will be recorded before drug administration (0 month) and after every two months till the completion of trial (0, 2M, 4th, 6th, i.e. the end of the treatment). The B.M.D. will be done before and after the completion of the treatment.

Subjective Assess:

Objective Assess:

IX. Study Evaluation Schedule

X. CRITERIA FOR WITHDRAWAL

During the course of the trial there may be certain potential adverse reactions like Kidney stones, hypocalcaemia with renal insufficiency (milk alkali syndrome) and interference of calcium with other essential nutrients. If any other side effects and other symptoms are observed then the trial drugs will be withdrawn and will be treated symptomatically.

 XI. CRITERIA FOR ASSESMENT

30% or more in B.M.D. T. Score (above —1.5 level) increase will be considered as significant improvement. .

Primary efficacy parameter………….Change in BMD

Secondary efficacy parameters………Change in symptom score

Percentage change is calculated as II BMD  -  I BMD x 100

   I BMD

= (%) percentage change.

Absolute change is calculated as (II BMD – I BMD)

XII. STATISTICAL ANALYSIS

Data on BMD T-Score will be analyzed using appropriate statistical tools. (Null Hypothesis: There is no significant difference between the BMD T-score in the treated group and control group).

XIII.  TRIAL MONITORING

SUDHATATVA, PHARMACY will monitor the progress of the trial     

XIV. ETHICAL REVIEW

Clearance certificate from Institutional Ethical Committee (IEC) or Head of the Institution should be obtained before the Project is initiated. IEC/Head of the Institution should submit patient’s information sheet and informed consent form along with project proposal for approval. Both of these forms should be maintained in duplicate with one copy given to the patient at the time of entry to the trial.

XV. TRAINING TO INVESTIGATORS AND PERSONS INVOLVED

Short-term two-day training will be provided to the Investigators and Laboratory personnel involved in the trial at CCRAS Hqrs. The investigators and technicians will be detailed about the clinical trial conduct and laboratory procedures in order to maintain the uniformity.

XVI. LABORATORY INVESTIGATIONS