Clinical Trial To Study The Effect Of Ayurvedic Treatment In The Management Of Diabetic Nephropathy.

Diabetic kidney disease (DKD) also referred to as diabetic nephropathy. The patients with diabetes and chronic kidney disease (CKD) presented a unique cohort of DKD population, which is identified by elevated urine albumin excretion or reduced glomerular filtration rate (GFR) or both.1 It affects the kidney function and alters the usual process of removal of waste products and excess fluid from the body. Sign and symptoms of kidney disease in people with diabetes include albuminuria (excretion of albumin in the urine), weight gain, swelling of ankle and legs, frequent urination in the night, morning sickness, anaemia, and high blood pressure.

Chronic kidney disease (CKD) also known as chronic Renal failure (CRF), is progressive loss in kidney function over a period of months or years. The symptoms of worsening kidney function are not specific and might include feeling generally unwell. The definition of chronic kidney disease has been simplified over the last 5 years. Diabetic nephropathy is a serious complication of type 1 diabetes and type 2 diabetes. Diabetic nephropathy affects the kidney ability to do their usual work of removing waste products and extra fluid from your body. The best way to prevent or delay diabetic nephropathy is by maintaining a healthy lifestyle and adequately managing your diabetes and high blood pressure.

The National Kidney Foundation - Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) working group has defined CKD as - The presence of markers of kidney damage for more than 3 months, as defined by structural or functional abnormalities of the kidney with or without decreased glomerular filtration rate (GFR), manifest by either pathological abnormalities or other marker of kidney damage, including in the composition of blood or urine or abnormalities in the imaging tests; or The presence of GFR less than 60 ml/1.73 m2 for more than 3 months with or without other signs of kidney damage.

RESEARCH QUESTION : Whether Ayurvedic treatment protocol, incorporating Sodhana and Shamana Chikitsa, is clinically effective for patients of Diabetic Nephropathy?

AIMS: To assess the clinical effect of Ayurvedic treatment for patients of Diabetic Nephropathy.

OBJECTIVES

•       **Primaryobjective-**To find out the effect of Ayurvedic treatment on the changes of eGFR and other kidney functions in the patients of DN.

•       **Secondary****objective-**To determine the effect of Ayurvedic treatment in DN symptoms and reducing the severity of DN.

HYPOTHESIS

Null**Hypothesis****(H0):**Ayurvedic treatment does not have effect in the management of  Diabetic Nephropathy.

Alternative Hypothesis (H1): Ayurvedic treatment has effect in the management of                         Diabetic Nephropathy.

DIAGNOSTIC CRITERIA

Criteria for DN: Either of the following present for > 3 months

|Markers of****kidney damage

(one or more)

·       Albuminuria (ACR > 300mg/g)

·       Urine sediment abnormalities

·       Electrolyte and other abnormalities due to tubular disorders.

·       Raised serum creatinine and blood urea level

·       Structural abnormalities detected by USG KUB (if necessary for confirmation or differential diagnosis)

·       History of kidney transplantation.

·      Decrease GFR (GFR < 60ml/min/1.73 m2)

**Study Design:**The present study is supposed to be-

 o   Level of study : Department of Kayachikitsa, National Institute of Ayurveda,Jaipur - 302002

o   Study type       : Interventional ,Single ,Randomized Comparative clinical

o   Method of Randomization: Computer generated randomization

o   Purpose                      : Treatment

o   Masking                     : Open label

o   Timing                        : Prospective

o   End point                   : Efficacy

o   Number of groups     : Single

   o Number of patients    :      30       o   Duration of study      : 60 days Administration of Drug:

Study time

Interventions

Dose

Timing

|3 Days

Gandharvahastadi eranda                              Sneha

40 ml at night

At bed time (After meals)

|16 Days (Day 4 to Day19)

Mutravirechaniya mahakashaya niruha basti

Dhanvantara Taila anuvasana basti (Kaala Krama)

 500 ml Niruha basti, 120 ml Anuvasana basti

Niruha basti – (Empty Stomach) Anuvasana Basti (After meals)

|Day 4 to Day 60

Punarnavashtaka Kwatha

40 ml two times a day

(30 min. Before meals)

| Gokshuradi Guggulu

2 Vati each of 250 mg, three times a day, with lukewarm water

(30 min. After meals)

| Punarnavaddi Mandura

2 Vati each of 125 mg, two times a day, with Punarnavashtaka

Kwatha

(30 min. Before meals)

| Rasayana Ghan Vati

2 Vati each of 250 mg, two times a day,

with lukewarm water

(30 min. After meals)

Duration of clinical trial and follow study

o   Total duration of trail for - 60 days

o   Follow up – After completion of the treatment, all the patients will be followed up every 2 weeks in OPD to observe further changes in anaemia profile of the disease. All above oral medicaments will be continued during follow up period.

Criteria for withdrawal

•       During the course of trial if any serious condition or any serious adverse effects of occur which required urgent treatment Patient himself wants to withdraw from the clinical trial.

•       Individuals who are unable or unwilling to comply with the study procedures and follow-up visits.

•       Patients complaining of any adverse reaction or severe complications or any other symptoms of intolerance will be withdrawn from the study.

Criteria of Assessment:

•       Subjective Criteria:•       Breathlessness (Shvasakrichchhrita)

•       Anorexia (Aruchi)

•       Oedema (Shotha )

•       Generalised Weakness (Daurbalya )

•       Nausea/Vomiting ( Chhardi )

•       Amount of urine ( Mutra Parimana )

·      Objective parametersThe following investigation will be done on 1 day and end of the trial. Following  laboratory investigations will be performed for proper diagnosis and to rule outmajor pathologicalconditions: 

Name of the investigation

Timing for investigation

|CBC

Baseline and After 8 weeks treatment

|LFT

Baseline and After 8 weeks treatment

|RFT

Baseline and After 8 weeks treatment

|LIPID PROFILE

Baseline and After 8 weeks treatment

|SERUM ELECTROLYTES

Baseline and After 8 weeks treatment

|URINE****ANALYSIS

Baseline and After 8 weeks treatment

|FBS, PPBS & HbA1C

Baseline and After 8 weeks treatment

Statistical Analysis:

The information will be gathered on the basis of observation made about various parameters will be subjected to statistical analysis in terms of Mean, Standard deviation and Standard error (SE). In Stat Graph Pad 3 software will be used & For Non-parametric Data Wilcox-on matched-pairs signed ranks test will be used, while for Parametric Data Paired ‘t’ Test will be used and results will be calculated. Paired t test will be carried out at p<0.05, p<0.01, p<0.001.

For inter-group comparisons, for the Non-parametric variables will be used Mann- Whitney Test, while for Parametric variables Unpaired ‘t’ Test will be used for statically analysis. The results will be calculated.

•         Non-significant      : P >0.05

•         Significant              : P <0.05

•         Highly significant    : P < 0.01, P < 0.001, P< 0.0001

 STUDY OUTCOMES

PRIMARY OUTCOME **-**Changes in Renal Function Test from baseline value at the end of 8thweek.

SECONDARY OUTCOME -

â—‰      Changes in Fasting blood sugar levels and HbA1c levels from baseline value at the end of 8th week.

â—‰      Changes in Hb level from baseline value at the end of 8th week.

â—‰      Changes in Urine output levels from baseline value at the end of 8th week.

â—‰      Changes in Symptoms of DN from baseline value at the end of 8th week.