Efficacy Study of Andrographis Paniculata Purified Standardized Extract (ApE) in Patients With Multiple Sclerosis (MS)

NCT02280876 | Completed Phase 1 DMC

• 2 other identifiers: PaCRU-02/PCNS.EM/12PCNS-EM
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the efficacy of ApE coated tablets, on the relapse rate in a group of relapsing remitting multiple sclerosis (RRMS) patients, as compared to a placebo group in a period of 12 months. This study will also determine the safety and tolerability of the drug administered over interferon beta vs. administration of a placebo formulation (also over interferon) during the evaluation period. Response will be assessed and measured by daily self patient recording, monthly clinical neurologist, and every three months serological and magnetic resonance parameters. Place of Study: National study in Chile with one center at the Regional Hospital in the city of Valdivia, including 30 patients enrolled by their respective neurologists.

Conditions

Multiple Sclerosis, Relapsing-Remitting

Keywords

MS; Demyelinating Autoimmune Diseases; CNS; Nervous System Diseases

Outcome Measures

Primary Outcomes (1)

• Clinical inflammatory (stamina) and disability score parameters (sensorial, neurosensitive, neuromotor and cognitive function) in patients with RRMS, treated with ApE and placebo administered over beta interferon.

  Clinical parameters (stamina, sensorial, neurosensitive, neuromotor and cognitive function), will be measured by the Fatigue Severity Scale (FSS) and Expanded Disability Scale (EDSS) in patients with RRMS treated with ApE and placebo.

  12 months

Secondary Outcomes (1)

• Safety, tolerability and efficacy of ApE and placebo administered over beta interferon in RRMS treated patients (adverse symptoms, general clinical laboratory and comparative statistical parameters)

  12 months

Other Outcomes (2)

• Central Nervous System (CNS) local inflammatory activity and anatomical damage parameters (functional and structural lesions) in RRMS patients treated with ApE and placebo administered over beta interferon.

  12 months

• Plasmatic inflammatory activity parameters (cytokines) in RRMS patients treated with ApE and placebo administered over beta interferon.

  12 months

Study Arms (2)

1 - Andrographis paniculata p/st extract

ACTIVE COMPARATOR

1 - Andrographis paniculata extract. Active comparator, consists of 15 adult patients with active Recurrent Remitting Multiple Sclerosis, randomly assigned, taking the active test product (Andrographis paniculata p/st extract, oral lozenges, one BID, for 12 months), in addition to base medication (Interferon).

Drug: 1 - Andrographis paniculata p/st extract

2 - Excipients

PLACEBO COMPARATOR

2 - Excipients. Placebo comparator, consists of 15 adult patients with active Recurrent Remitting Multiple Sclerosis, randomly assigned, taking the placebo formulation (Only the excipients of the active test product, in oral lozenges of same shape, one BID, for 12 months), in addition to base medication (Interferon).

Drug: 2 - Excipients

Interventions

1 - Andrographis paniculata p/st extract DRUG

Andrographis paniculata Extract (ApE), Oral tablets 650 mg, with 170 mg. of andrographolides active principles, three times per day, during a total of 365 continuous days. Other Names: • ApE tablets, EUROMED Specific. Santiago Chile.

Also known as: Andrographolide, Verum formulation, Andrographis paniculata Extract ( ApE ), Paractin®

1 - Andrographis paniculata p/st extract

2 - Excipients DRUG

Placebo 650mg tabs, 2/day, 365 days continuously. Other Names: • Excipients tablets EUROMED Specific. Santiago Chile

Also known as: Placebo formulation

2 - Excipients

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients diagnosed with MS according to McDonald scale
• Relapsing Remitting Forms of MS (subtypes of Lublin)
• Minor or less incapacity according to EDSS scale
• At least one relapse in the last 2 years
• Sign an informed consent

You may not qualify if:

• Primary and Secondary Progressive MS patients.
• Use of corticosteroids up to one month previous to enrollment
• Use of immunosuppressors up to one month previous to enrollment
• Use of drugs that induce hepatic metabolism
• Pregnancy, contraception, breast feeding.
• Psychiatric disorders
• Systemic diseases
• Chronic renal failure
• Diabetes mellitus
• Cardiac failure
• Respiratory failure
• Cancer

Sponsors & Collaborators

• Universidad Austral de Chile: lead
• Comisión Nacional de Investigación Científica y Tecnológica: collaborator
• University of Chile: collaborator

Study Sites (1)

Hospital Regional

Valdivia, Los Ríos Region, 5090000, Chile

Location

Related Publications (18)

• Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple sclerosis. N Engl J Med. 2000 Sep 28;343(13):938-52. doi: 10.1056/NEJM200009283431307. No abstract available.

  PMID: 11006371 BACKGROUND

• Wingerchuk DM, Lucchinetti CF, Noseworthy JH. Multiple sclerosis: current pathophysiological concepts. Lab Invest. 2001 Mar;81(3):263-81. doi: 10.1038/labinvest.3780235.

  PMID: 11310820 BACKGROUND

• Galboiz Y, Miller A. Immunological indicators of disease activity and prognosis in multiple sclerosis. Curr Opin Neurol. 2002 Jun;15(3):233-7. doi: 10.1097/00019052-200206000-00002.

  PMID: 12045718 BACKGROUND

• Phillips JT, Rice G, Frohman E, Vande Gaer L, Scott T, Haas J, Eggenberger E, Freedman MS, Stuart W, Cunha L, Jacobs L, Oger J, Arnold D, Murray TJ, DiBiase M, Jethwa V, Goelz S. A multicenter, open-label, phase II study of the immunogenicity and safety of a new prefilled syringe (liquid) formulation of Avonex in patients with multiple sclerosis. Clin Ther. 2004 Apr;26(4):511-21. doi: 10.1016/s0149-2918(04)90053-7.

  PMID: 15189748 BACKGROUND

• Iruretagoyena MI, Tobar JA, Gonzalez PA, Sepulveda SE, Figueroa CA, Burgos RA, Hancke JL, Kalergis AM. Andrographolide interferes with T cell activation and reduces experimental autoimmune encephalomyelitis in the mouse. J Pharmacol Exp Ther. 2005 Jan;312(1):366-72. doi: 10.1124/jpet.104.072512. Epub 2004 Aug 26.

  PMID: 15331658 BACKGROUND

• Rajagopal S, Kumar RA, Deevi DS, Satyanarayana C, Rajagopalan R. Andrographolide, a potential cancer therapeutic agent isolated from Andrographis paniculata. J Exp Ther Oncol. 2003 May-Jun;3(3):147-58. doi: 10.1046/j.1359-4117.2003.01090.x.

  PMID: 14641821 BACKGROUND

• Calabrese C, Berman SH, Babish JG, Ma X, Shinto L, Dorr M, Wells K, Wenner CA, Standish LJ. A phase I trial of andrographolide in HIV positive patients and normal volunteers. Phytother Res. 2000 Aug;14(5):333-8. doi: 10.1002/1099-1573(200008)14:53.0.co;2-d.

  PMID: 10925397 BACKGROUND

• Hidalgo MA, Romero A, Figueroa J, Cortes P, Concha II, Hancke JL, Burgos RA. Andrographolide interferes with binding of nuclear factor-kappaB to DNA in HL-60-derived neutrophilic cells. Br J Pharmacol. 2005 Mar;144(5):680-6. doi: 10.1038/sj.bjp.0706105.

  PMID: 15678086 BACKGROUND

• Burgos RA, Hidalgo MA, Monsalve J, LaBranche TP, Eyre P, Hancke JL. 14-deoxyandrographolide as a platelet activating factor antagonist in bovine neutrophils. Planta Med. 2005 Jul;71(7):604-8. doi: 10.1055/s-2005-871264.

  PMID: 16041644 BACKGROUND

• Burgos RA, Seguel K, Perez M, Meneses A, Ortega M, Guarda MI, Loaiza A, Hancke JL. Andrographolide inhibits IFN-gamma and IL-2 cytokine production and protects against cell apoptosis. Planta Med. 2005 May;71(5):429-34. doi: 10.1055/s-2005-864138.

  PMID: 15931581 BACKGROUND

• Coon JT, Ernst E. Andrographis paniculata in the treatment of upper respiratory tract infections: a systematic review of safety and efficacy. Planta Med. 2004 Apr;70(4):293-8. doi: 10.1055/s-2004-818938.

  PMID: 15095142 BACKGROUND

• Thamlikitkul V, Dechatiwongse T, Theerapong S, Chantrakul C, Boonroj P, Punkrut W, Ekpalakorn W, Boontaeng N, Taechaiya S, Petcharoen S, et al. Efficacy of Andrographis paniculata, Nees for pharyngotonsillitis in adults. J Med Assoc Thai. 1991 Oct;74(10):437-42.

  PMID: 1797953 BACKGROUND

• Caceres DD, Hancke JL, Burgos RA, Wikman GK. Prevention of common colds with Andrographis paniculata dried extract. A Pilot double blind trial. Phytomedicine. 1997 Jun;4(2):101-4. doi: 10.1016/S0944-7113(97)80051-7.

  PMID: 23195395 BACKGROUND

• Cabrera D, Gutierrez J, Cabello-Verrugio C, Morales MG, Mezzano S, Fadic R, Casar JC, Hancke JL, Brandan E. Andrographolide attenuates skeletal muscle dystrophy in mdx mice and increases efficiency of cell therapy by reducing fibrosis. Skelet Muscle. 2014 Mar 21;4:6. doi: 10.1186/2044-5040-4-6. eCollection 2014.

  PMID: 24655808 BACKGROUND

• Caceres DD, Hancke JL, Burgos RA, Sandberg F, Wikman GK. Use of visual analogue scale measurements (VAS) to asses the effectiveness of standardized Andrographis paniculata extract SHA-10 in reducing the symptoms of common cold. A randomized double blind-placebo study. Phytomedicine. 1999 Oct;6(4):217-23. doi: 10.1016/S0944-7113(99)80012-9.

  PMID: 10589439 BACKGROUND

• Gabrielian ES, Shukarian AK, Goukasova GI, Chandanian GL, Panossian AG, Wikman G, Wagner H. A double blind, placebo-controlled study of Andrographis paniculata fixed combination Kan Jang in the treatment of acute upper respiratory tract infections including sinusitis. Phytomedicine. 2002 Oct;9(7):589-97. doi: 10.1078/094471102321616391.

  PMID: 12487322 BACKGROUND

• Burgos RA, Hancke JL, Bertoglio JC, Aguirre V, Arriagada S, Calvo M, Caceres DD. Efficacy of an Andrographis paniculata composition for the relief of rheumatoid arthritis symptoms: a prospective randomized placebo-controlled trial. Clin Rheumatol. 2009 Aug;28(8):931-46. doi: 10.1007/s10067-009-1180-5. Epub 2009 Apr 29.

  PMID: 19408036 BACKGROUND

• Bertoglio JC, Baumgartner M, Palma R, Ciampi E, Carcamo C, Caceres DD, Acosta-Jamett G, Hancke JL, Burgos RA. Andrographis paniculata decreases fatigue in patients with relapsing-remitting multiple sclerosis: a 12-month double-blind placebo-controlled pilot study. BMC Neurol. 2016 May 23;16:77. doi: 10.1186/s12883-016-0595-2.

  PMID: 27215274 RESULT

Related Links

• María A. Hidalgo, Juan L. Hancke, Juan C. Bertoglio and Rafael A. Burgos. Andrographolide, a New Potential Drug for the Long Term Treatment of Rheumatoid Arthritis Disease. Innovative Rheumatology. International standard book (ISBN) 978-953-51-0916-7

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting; Nervous System Diseases

Interventions

andrographolide; Andrographis paniculata extract

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Juan L. Hancke, PhD

  Universidad Austral de Chile

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Clinical Investigator

Study Record Dates

• First Submitted: October 20, 2014
• First Posted: November 3, 2014
• Study Start: January 1, 2012
• Primary Completion: February 1, 2015
• Study Completion: May 1, 2015
• Last Updated: June 23, 2016

Record last verified: 2016-01

Data Sharing

• IPD Sharing: Will share

Locations

CL (1)