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

NCT ID: NCT02273635

Last Updated: 2014-10-27

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

UNKNOWN

Clinical Phase

PHASE1/PHASE2

Total Enrollment

68 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-09-30

Study Completion Date

2017-04-30

Brief Summary

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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.

Detailed Description

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1. Evaluate the clinical efficacy of andrographolide 140 mg administered orally twice a day versus a placebo in:

* Delay in the disability capacity progression through the Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC) at 24 months compared to the baseline.
* Delay in cognitive impairment by means of Paced Auditory Serial Addition Test (PASAT), Symbol Digit Modalities Test (SDMT) and depression (Beck) at 24 months compared to the baseline.
* Quality of life Multiple Sclerosis Impact Scale (MSIS 29) and fatigue (Krupp) through parameters reported by the patients at at 24 months compared to the baseline.
* Tolerability of andrographolide measured by the Treatment Satisfaction Questionnaire for Medication (TSQM) at 24 months.
* Delay in the decrease in brain volume measured by Magnetic Resonance (MR) at 24 months compared to the baseline.
* Number and volume of new lesions or larger size in T2 by MR at 24 months compared to the baseline.
* Number of new hipointense lesions in T1 or (gadolinium captive) by MR at 24 months compared to the baseline.
* Delay in the retineal thinning measured by Optical Coherence Tomography (OCT) and visual field at 24 months compared to the baseline.
* Safety of andrographolide at 24 months through the record of adverse effects in symptom dairy and programmed interviews.
2. Explore the pharmacokinetic of andrographolide 140 mg administered orally twice day in:

* bio availability and concentration of andrographolide in the patients with treatment.
* half-life, maximum concentration, clearance of andrographolide in equilibrium state.
3. Determine the immunomodulatory effects of andrographolide 140 mg administered twice a day orally on lymphocyte populations in patients through the:

* Determination of Th1, Th2, Th17 and Treg lymphocyte sub-populations.
* Determination of cytokines IFNgama, TNFalpha, IL2, IL17alpha and TGFbeta.

Population: adult patients, men and women with progressive forms of MS. The number of patients to be selected will be 68, to randomly assign 34 patients to each group.

Conditions

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Primary Progressive Multiple Sclerosis Multiple Sclerosis, Secondary Progressive

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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andrographolides

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

Group Type EXPERIMENTAL

Andrographolides

Intervention Type DRUG

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

sugar tablets

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

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

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

Interventions

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placebo

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

Intervention Type DRUG

Andrographolides

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

Intervention Type DRUG

Other Intervention Names

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andrographolide, neoandrographolide, deoxyandrographolide IB-MS 14

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pontificia Universidad Catolica de Chile

OTHER

Sponsor Role collaborator

University of Chile

OTHER

Sponsor Role collaborator

Universidad Austral de Chile

OTHER

Sponsor Role collaborator

Innobioscience SpA

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Juan L Hancke, DVM, PhD

Role: STUDY_DIRECTOR

Universidad Austral de Chile

Locations

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Multiple Sclerosis Centre, Pontificia Universidad Catolica de Chile

Santiago, Santiago Metropolitan, Chile

Site Status RECRUITING

Countries

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Chile

Central Contacts

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Claudia A Carcamo, MD, PhD

Role: CONTACT

+56223546885

Ethel L Ciampi, MD

Role: CONTACT

+56223546885

Facility Contacts

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Claudia A Carcamo, MD, PhD.

Role: primary

56 2 3546885

Ana C Reyes, Nurse

Role: backup

56 2 3546885

References

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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.

Reference Type BACKGROUND
PMID: 15331658 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16597709 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19408036 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24655808 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19038244 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15931581 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15678086 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23044768 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21114791 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32380977 (View on PubMed)

Other Identifiers

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14-391

Identifier Type: OTHER

Identifier Source: secondary_id

14PIE-26946CORFO

Identifier Type: -

Identifier Source: org_study_id

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