Clinical trial NCT02107469: A Study of Phyllanthus Niruri and Sida Cordifolia in Diabetic Peripheral Polyneuropathy
Official title: A Randomized Placebo-compared Study on Efficiency of Two Different Administration Forms of Phyllanthus Niruri and Sida Cordifolia in Patients With Diabetic Peripheral Polyneuropathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetic Polyneuropathy
Diabetic Neuralgia
Diabetic Neuropathies
Diabetic Neuropathy
Keywords: Diabetic Polyneuropathy
Diabetic
Polyneuropathy
Ayurvedic
Ayurveda
Neuralgia
Diabetic Neuralgia
Sida cordifolia
Phyllanthus Niruri
Phyllanthus Amarus
Extracts
Extract
Crude Herb
Crude
Herb
Herbal
Herbal Extract
Decoction
Churna
Powder
Bala
Bhumyamalaki
Tamalaki
Lead sponsor: Rosenberg European Academy of Ayurveda
Sponsor class: OTHER
Collaborators: name: EUROPEAN PROFESSIONAL ASSOCIATION OF AYURVEDA PRACTITIONERS AND THERAPISTS
First posted: 2014-04-08
Enrollment: 98
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to determine whether phyllanthus niruri and sida cordifolia are effective in treatment of diabetic polyneuropathy compared to placebo. Also two different administration forms (extract capsules and crude herbs) are used to find out whether there are differences in efficiency and compliance.

Detailed description: This study will explore the difference in therapeutic efficiency between modern extracts and whole drug powder of Phyllanthus niruri plus Sida cordifolia root decoction in diabetic neuropathy compared to placebo. The difference in compliance regarding medicine and food recommendations will be additionally documented.

Design - Study in two parts:

Part I: prospective, placebo-controlled, partly double-blinded (regarding 2 of the arms- all arms are investigator-blinded), 3 arm-parallel group study for 3 weeks Part II: prospective, investigator-blinded, long-term-study for 8 weeks. The active groups of part I will continue with their assigned medication and the placebo-patients of part I will be randomized again for the 2 groups of active medication.

Methods:

Symptoms will be assessed using Neuropathy total symptom score 6 (NTSS-6) as main primary parameter. Additional quantitative sensory testing will be done with the Neuropathy Analyzer Vibrotherm Dx from Diabetic Footcare India for detection of vibration and thermal sensation threshold. Tolerability, adverse drug reactions, Compliance regarding medication intake and dietary recommendations will be documented by an additional questionnaire.

Three randomized groups of 30 outpatients each (powder/decoction ; extract ; placebo) will be created for the part I of the study for the first 3 weeks.

At part I placebo group will be double blinded compared to extract group and investigator-blinded to powder/decoction group.

After 3 weeks the patients of the placebo group will be randomly assigned into both active treatment groups for part II to describe the course of treatment with both administration forms with 45 patients each.

Study visits will be prior and after 1,2,3,5 and 8 weeks.

Statistical plan: The primary parameter will be compared by Mann Whitney-U-Test.

Secondary Parameters will be descriptively analysed.

Implication:

A new herbal formulation will be tested for diabetic neuropathy with modern randomized placebo controlled study design in Part I. The outcome of the observation in part II will bring us closer to evidence based selection of different ayurvedic preparations in an upraising marked of new extraction technologies.

Registry procedures and other quality factors:

Data checks to compare data entered into the registry against predefined rules for range or consistency with other data fields in the registry.

Source data verification to assess the accuracy, completeness, or representativeness of registry data by comparing the data to external data sources (medical records, paper case report forms).

Standard Operating Procedures to address registry operations and analysis activities, such as patient recruitment, data collection, data management, data analysis, reporting for adverse events, and change management.

Sample size assessment to specify the number of participants or participant years necessary to demonstrate an effect.

Statistical analysis plan describing the analytical principles and statistical techniques to be employed in order to address the primary and secondary objectives, as specified in the study protocol or plan.

Eligibility criteria: Inclusion Criteria:

* Signed consent form
* positive history of type 1 or 2 diabetes mellitus having the symptoms of diabetic neuropathy (sensory, peripheral) will be selected.
* Only outpatient setting will be included.
* Patients with ≥2 symptoms having at least one symptom with moderate severity in occasional frequency (3 points in NTSS-6) are included if they additionally show an impaired vibration detection threshold.

Exclusion Criteria:

* suffering from any other associated clinical conditions influencing peripheral nerve function, for example:
* peripheral vascular disease if reason for nerve damage
* vitamin deficiency (FOL,B12,E)
* heavy metal intoxication (especially with lead, cadmium and thallium)
* other intoxications (alcohol, medicine)
* infectious disease (like HIV, typhus, syphilis, lyme disease, mononucleosis,...)
* cancer
* autoimmune disease
* hepatitis
* vasculitis
* amyloidosis
* severe kidney failure
* pregnancy
* disorder of connective tissue
* steroids taken up to 1 month prior to study
* the likely need for insulin therapy

Regarding prior medication patients are advised not to start additional therapy during the study as long as symptoms are not worsening, antihyperglycaemic drugs will only be adjusted by study physicians if necessary.

Primary outcomes:
measure: Improvement of NTSS-6 SCORE in per cent from baseline
timeFrame: Initially, after 1, 2, 3, 5, 8 weeks of treatment, where placebo group will start again in one of the herbal treatment groups after 3 weeks (9 instead of 6 assessments)
Secondary outcomes:
measure: Improvement from baseline in per cent of quantitative sensory testing of vibration and thermal (hot/cold) threshold (score)
timeFrame: Initially, after 1, 2, 3, 5, 8 weeks of treatment, where placebo group will start again in one of the herbal treatment groups after 3 weeks (9 instead of 6 assessments)
measure: Assessment of compliance regarding medication and dietary recommendations (score).
timeFrame: After 1, 2, 3, 5, 8 weeks of treatment, where placebo group will start again in one of the herbal treatment groups after 3 weeks (8 instead of 5 assessments)
Other outcomes:
measure: Patient Diary
timeFrame: From start to end of treatment (8 weeks, 11 weeks for placebo group)
Locations:
city: Nadiad
country: India
facility: P.D. Patel Ayurveda Hospital
state: Gujarat
Study officials:
affiliation: P.D. Patel Ayurveda Hospital / Rosenberg European Academy of Ayurveda
name: Shivenarain N. Gupta, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
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