Efficacy, Safety and Tolerability of Andrographolides Versus Placebo in Patients With Progressive Forms of MS

NCT02273635 | Unknown Phase 1 DMC

• 2 other identifiers: 14PIE-26946CORFO14-391
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to compare the efficacy and safety of andrographolide 140 mg administered twice a day orally versus a placebo as a modifying treatment of the disease in patients with the progressive forms of Multiple Sclerosis (MS). The principal outcome is to determine the efficacy, of andrographolide in retarding the progression of brain atrophy in patients with progressive forms of MS.

Conditions

Primary Progressive Multiple Sclerosis; Multiple Sclerosis, Secondary Progressive

Outcome Measures

Primary Outcomes (1)

• Brain atrophy in patients with progressive forms of MS

  Retarding the progression of brain atrophy as measured by MR quantified by the percentage of change in volume size utilizing SIENA.

  24 months

Secondary Outcomes (15)

• Expanded Disability Status Scale (EDSS)

  24 months

• Paced Auditory Serial Addition Test (PASAT)

  24 months

• Quality of life Multiple Sclerosis Impact Scale (MSIS 29)

  24 months

• Treatment Satisfaction Questionnaire for Medication (TSQM)

  24 months

• Number of new T2 lesions

  24 months

Study Arms (2)

andrographolides

EXPERIMENTAL

Coated tablets containing 140 mg andrographolides twice a day orally administered for a period of 24 months.

Drug: Andrographolides

sugar tablets

PLACEBO COMPARATOR

Coated tablets containing 140 mgs excipients twice a day orally administered for a period of 24 months.

Drug: placebo

Interventions

Andrographolides DRUG

140 mg andrographolides coated tablets twice a day orally administered for 24 months.

Also known as: andrographolide, neoandrographolide, deoxyandrographolide, IB-MS 14

andrographolides

placebo DRUG

140 mg excipients coated tablets twice a day orally administered for 24 months

sugar tablets

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Informed Consent previous to the initiation of the study before any evaluation.
• Men and women \> 18 years of age with Minimental \> 24.
• Patients with diagnosis of secondary progressive MS without relapses or primary progressive MS according to the criteria of McDonald 2010.

You may not qualify if:

• Relapsing-remitting MS
• Current Immunomodulatory or immunosuppressive therapy
• Uncontrolled systemic diseases not controlled or treated with immunotherapy (i.e Rheumatoid Arthritis, Lupus Erythematosus).
• Pregnant women

Sponsors & Collaborators

• Innobioscience SpA: lead
• Pontificia Universidad Catolica de Chile: collaborator
• University of Chile: collaborator
• Universidad Austral de Chile: collaborator

Study Sites (1)

Multiple Sclerosis Centre, Pontificia Universidad Catolica de Chile

Santiago, Santiago Metropolitan, 8330033, Chile

RECRUITING

Related Publications (10)

• 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

• Iruretagoyena MI, Sepulveda SE, Lezana JP, Hermoso M, Bronfman M, Gutierrez MA, Jacobelli SH, Kalergis AM. Inhibition of nuclear factor-kappa B enhances the capacity of immature dendritic cells to induce antigen-specific tolerance in experimental autoimmune encephalomyelitis. J Pharmacol Exp Ther. 2006 Jul;318(1):59-67. doi: 10.1124/jpet.106.103259. Epub 2006 Apr 5.

  PMID: 16597709 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

• 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

• Carretta MD, Alarcon P, Jara E, Solis L, Hancke JL, Concha II, Hidalgo MA, Burgos RA. Andrographolide reduces IL-2 production in T-cells by interfering with NFAT and MAPK activation. Eur J Pharmacol. 2009 Jan 14;602(2-3):413-21. doi: 10.1016/j.ejphar.2008.11.011. Epub 2008 Nov 13.

  PMID: 19038244 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

• 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

• Sandborn WJ, Targan SR, Byers VS, Rutty DA, Mu H, Zhang X, Tang T. Andrographis paniculata extract (HMPL-004) for active ulcerative colitis. Am J Gastroenterol. 2013 Jan;108(1):90-8. doi: 10.1038/ajg.2012.340. Epub 2012 Oct 9.

  PMID: 23044768 BACKGROUND

• Tang T, Targan SR, Li ZS, Xu C, Byers VS, Sandborn WJ. Randomised clinical trial: herbal extract HMPL-004 in active ulcerative colitis - a double-blind comparison with sustained release mesalazine. Aliment Pharmacol Ther. 2011 Jan;33(2):194-202. doi: 10.1111/j.1365-2036.2010.04515.x. Epub 2010 Nov 30.

  PMID: 21114791 BACKGROUND

• Ciampi E, Uribe-San-Martin R, Carcamo C, Cruz JP, Reyes A, Reyes D, Pinto C, Vasquez M, Burgos RA, Hancke J. Efficacy of andrographolide in not active progressive multiple sclerosis: a prospective exploratory double-blind, parallel-group, randomized, placebo-controlled trial. BMC Neurol. 2020 May 7;20(1):173. doi: 10.1186/s12883-020-01745-w.

  PMID: 32380977 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis, Chronic Progressive

Interventions

andrographolide; neoandrographolide

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Juan L Hancke, DVM, PhD

  Universidad Austral de Chile

  STUDY DIRECTOR

Central Study Contacts

Claudia A Carcamo, MD, PhD

CONTACT

+56223546885; ccarcamo@med.puc.cl

Ethel L Ciampi, MD

CONTACT

+56223546885; anticsnap@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2014
• First Posted: October 24, 2014
• Study Start: September 1, 2014
• Primary Completion: November 1, 2016
• Study Completion: April 1, 2017
• Last Updated: October 27, 2014

Record last verified: 2014-10

Locations

CL (1)