A Study of Phyllanthus Niruri and Sida Cordifolia in Diabetic Peripheral Polyneuropathy

NCT ID: NCT02107469

Last Updated: 2016-02-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

98 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-06-30

Study Completion Date

2016-02-29

Brief Summary

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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

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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.

Conditions

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Diabetic Polyneuropathy Diabetic Neuralgia Diabetic Neuropathies Diabetic Neuropathy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Ancient herbal treatment

Phyllanthus niruri 3g fine dry powder 3 times a day with warm water before meals for 8 weeks

Sida cordifolia 7g coarse dry powder 2 times a day prepared as traditional decoction before meals for 8 weeks. Decoction: Take provided measurement cup full of water (112ml) and soak one portion (pe-packed) of the powder for 12 hours, then boil it until the upper level has been reduced to 1/4, filter, cool down to room temperature, drink

Group Type EXPERIMENTAL

Sida cordifolia roots

Intervention Type DRUG

Sida cordifolia roots, crude drug (coarse powder) a plant product 7g (packages prepared) are soaked in 112ml water (measurement cup provided) for 12 hours and then boiled until the level is reduced to 1/4 of hight. Fluid is filtered an drunk after cooling down to room temperature - orally 2 times a day before breakfast and dinner

Phyllanthus niruri

Intervention Type DRUG

Phyllanthus niruri (whole plant) fine powder 3g three times a day with warm water before meals taken orally.

Modern extract herbal treatment

Phyllanthus niruri extract 2 capsules 3 times a day with warm water before meals for 8 weeks

Sida cordifolia roots extract 2 capsules 2 times a day with warm water before meals for 8 weeks

Group Type EXPERIMENTAL

Sida cordifolia roots extract

Intervention Type DRUG

gelatine capsule with 300mg Sida cordifolia roots spraydry extract 12:1 concentrated normalized to alkaloids (alcoholic/aqueous extract) - 2 capsules taken orally 2 times a day with warm water before meal

Phyllanthus niruri extract

Intervention Type DRUG

gelatine capsule with 300mg Phyllanthus niruri spray dry extract 5:1 concentrated normalized to bitters (alcohol/aqueous extract) - 2 capsules taken orally 3 times a day with warm water before meal

Placebo

Phyllanthus niruri placebo 2 capsules 3 times a day with warm water before meals for 3 weeks

Sida cordifolia placebo 2 capsules 2 times a day with warm water before meals for 3 weeks

Group Type PLACEBO_COMPARATOR

Sida cordifolia placebo

Intervention Type OTHER

300mg inert Maltodextrin in gelatine capsule. 2 capsules given 2 times a day orally with warm water before meals

Phyllanthus niruri placebo

Intervention Type OTHER

300mg inert Maltodextrin in gelatine capsule. 2 capsules given 3 times a day orally with warm water before meals

Interventions

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Sida cordifolia roots

Sida cordifolia roots, crude drug (coarse powder) a plant product 7g (packages prepared) are soaked in 112ml water (measurement cup provided) for 12 hours and then boiled until the level is reduced to 1/4 of hight. Fluid is filtered an drunk after cooling down to room temperature - orally 2 times a day before breakfast and dinner

Intervention Type DRUG

Phyllanthus niruri

Phyllanthus niruri (whole plant) fine powder 3g three times a day with warm water before meals taken orally.

Intervention Type DRUG

Sida cordifolia roots extract

gelatine capsule with 300mg Sida cordifolia roots spraydry extract 12:1 concentrated normalized to alkaloids (alcoholic/aqueous extract) - 2 capsules taken orally 2 times a day with warm water before meal

Intervention Type DRUG

Phyllanthus niruri extract

gelatine capsule with 300mg Phyllanthus niruri spray dry extract 5:1 concentrated normalized to bitters (alcohol/aqueous extract) - 2 capsules taken orally 3 times a day with warm water before meal

Intervention Type DRUG

Sida cordifolia placebo

300mg inert Maltodextrin in gelatine capsule. 2 capsules given 2 times a day orally with warm water before meals

Intervention Type OTHER

Phyllanthus niruri placebo

300mg inert Maltodextrin in gelatine capsule. 2 capsules given 3 times a day orally with warm water before meals

Intervention Type OTHER

Other Intervention Names

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Bala moola Bala Phyllanthus amarus Bhumyamalaki Tamalaki Bala moola Bala Phyllanthus amarus Bhumyamalaki Tamalaki Placebo Inert maltodextrine Maltodextrine Placebo Inert Maltodextrin Maltodextrin

Eligibility Criteria

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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.
Minimum Eligible Age

20 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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EUROPEAN PROFESSIONAL ASSOCIATION OF AYURVEDA PRACTITIONERS AND THERAPISTS

UNKNOWN

Sponsor Role collaborator

Rosenberg European Academy of Ayurveda

OTHER

Sponsor Role lead

Responsible Party

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Prof. S.N. Gupta

Superintendent of P.D. Patel Ayurveda Hospital Nadiad, Gujarat, India

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Shivenarain N. Gupta, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

P.D. Patel Ayurveda Hospital / Rosenberg European Academy of Ayurveda

Locations

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P.D. Patel Ayurveda Hospital

Nadiād, Gujarat, India

Site Status

Countries

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India

References

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Asare GA, Addo P, Bugyei K, Gyan B, Adjei S, Otu-Nyarko LS, Wiredu EK, Nyarko A. Acute toxicity studies of aqueous leaf extract of Phyllanthus niruri. Interdiscip Toxicol. 2011 Dec;4(4):206-10. doi: 10.2478/v10102-011-0031-9.

Reference Type BACKGROUND
PMID: 22319255 (View on PubMed)

Bastyr EJ 3rd, Price KL, Bril V; MBBQ Study Group. Development and validity testing of the neuropathy total symptom score-6: questionnaire for the study of sensory symptoms of diabetic peripheral neuropathy. Clin Ther. 2005 Aug;27(8):1278-94. doi: 10.1016/j.clinthera.2005.08.002.

Reference Type BACKGROUND
PMID: 16199253 (View on PubMed)

Boulton AJ. The diabetic foot: from art to science. The 18th Camillo Golgi lecture. Diabetologia. 2004 Aug;47(8):1343-53. doi: 10.1007/s00125-004-1463-y. Epub 2004 Jul 28.

Reference Type BACKGROUND
PMID: 15309286 (View on PubMed)

Cornblath, DR. Diabetic neuropathy: Diagnostic methods. Advanced Studies in Medicine 4(8a):650-661, 2004.

Reference Type BACKGROUND

Dettori J. The random allocation process: two things you need to know. Evid Based Spine Care J. 2010 Dec;1(3):7-9. doi: 10.1055/s-0030-1267062. No abstract available.

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PMID: 22956922 (View on PubMed)

Grover JK, Yadav S, Vats V. Medicinal plants of India with anti-diabetic potential. J Ethnopharmacol. 2002 Jun;81(1):81-100. doi: 10.1016/s0378-8741(02)00059-4.

Reference Type BACKGROUND
PMID: 12020931 (View on PubMed)

Huber CS, Levett JM, Atkinson JM. A Tool to Assess Compliance in Anticoagulation Management. In: Henriksen K, Battles JB, Keyes MA, Grady ML, editors. Advances in Patient Safety: New Directions and Alternative Approaches (Vol. 3: Performance and Tools). Rockville (MD): Agency for Healthcare Research and Quality (US); 2008 Aug. Available from http://www.ncbi.nlm.nih.gov/books/NBK43677/

Reference Type BACKGROUND
PMID: 21249935 (View on PubMed)

Patel K, Patel M, Gupta SN. Effect of Atibalamula and Bhumyamalaki on thirty-three patients of diabetic neuropathy. Ayu. 2011 Jul;32(3):353-6. doi: 10.4103/0974-8520.93913.

Reference Type BACKGROUND
PMID: 22529650 (View on PubMed)

Kanth VR, Diwan PV. Analgesic, antiinflammatory and hypoglycaemic activities of Sida cordifolia. Phytother Res. 1999 Feb;13(1):75-7. doi: 10.1002/(SICI)1099-1573(199902)13:13.0.CO;2-F.

Reference Type BACKGROUND
PMID: 10189958 (View on PubMed)

Kastenbauer T, Sauseng S, Brath H, Abrahamian H, Irsigler K. The value of the Rydel-Seiffer tuning fork as a predictor of diabetic polyneuropathy compared with a neurothesiometer. Diabet Med. 2004 Jun;21(6):563-7. doi: 10.1111/j.1464-5491.2004.01205.x.

Reference Type BACKGROUND
PMID: 15154940 (View on PubMed)

Konate K, Bassole IH, Hilou A, Aworet-Samseny RR, Souza A, Barro N, Dicko MH, Datte JY, M'Batchi B. Toxicity assessment and analgesic activity investigation of aqueous acetone extracts of Sida acuta Burn f . and Sida cordifolia L. (Malvaceae), medicinal plants of Burkina Faso. BMC Complement Altern Med. 2012 Aug 11;12:120. doi: 10.1186/1472-6882-12-120.

Reference Type BACKGROUND
PMID: 22883637 (View on PubMed)

Kudom AA, Mensah BA, Botchey MA. Aqueous neem extract versus neem powder on Culex quinquefasciatus: implications for control in anthropogenic habitats. J Insect Sci. 2011;11:142. doi: 10.1673/031.011.14201.

Reference Type BACKGROUND
PMID: 22233153 (View on PubMed)

Kumar P. S., et al. Immediate effects of nerve sliders and nerve massage on vibration and thermal perception thresholds in patients with painful diabetic peripheral neuropathy- a pilot randomized clinical trial. Physiotherapy and Occupational Therapy Journal 3(3):5-19, July - Sept 2010

Reference Type BACKGROUND

Sumanth M, Mustafa SS. Antistress, Adoptogenic Activity of Sida cordifolia Roots in Mice. Indian J Pharm Sci. 2009 May;71(3):323-4. doi: 10.4103/0250-474X.56027.

Reference Type BACKGROUND
PMID: 20490305 (View on PubMed)

Neeraj, T., & Parul, S. (2011). Quality standards of indian medicinal plants. New Delhi: Indian Council of Medical Research, Medicinal Plants Unit.

Reference Type BACKGROUND

Shy ME, Frohman EM, So YT, Arezzo JC, Cornblath DR, Giuliani MJ, Kincaid JC, Ochoa JL, Parry GJ, Weimer LH; Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Quantitative sensory testing: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2003 Mar 25;60(6):898-904. doi: 10.1212/01.wnl.0000058546.16985.11.

Reference Type BACKGROUND
PMID: 12654951 (View on PubMed)

Smieja M, Hunt DL, Edelman D, Etchells E, Cornuz J, Simel DL. Clinical examination for the detection of protective sensation in the feet of diabetic patients. International Cooperative Group for Clinical Examination Research. J Gen Intern Med. 1999 Jul;14(7):418-24. doi: 10.1046/j.1525-1497.1999.05208.x.

Reference Type BACKGROUND
PMID: 10417599 (View on PubMed)

Srividya N, Periwal S. Diuretic, hypotensive and hypoglycaemic effect of Phyllanthus amarus. Indian J Exp Biol. 1995 Nov;33(11):861-4.

Reference Type BACKGROUND
PMID: 8786163 (View on PubMed)

Related Links

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http://www.nadiadayurveda.org

Nadiad Ayurveda College and Hospital - Site of study

http://www.ayurveda-akademie.org/en/home/

Sponsor - Rosenberg European Academy of Ayurveda

http://www.ayurveda-verband.eu/?L=1

Funding society: European Professional Association of Ayurveda-Practitioners and -Therapists

Other Identifiers

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NADIAD 2014

Identifier Type: -

Identifier Source: org_study_id

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