Efficacy, Safety and Tolerability of Andrographolides Versus Placebo in Patients With Progressive Forms of MS
Primary Purpose
Primary Progressive Multiple Sclerosis, Multiple Sclerosis, Secondary Progressive
Status
Unknown status
Phase
Phase 1
Locations
Chile
Study Type
Interventional
Intervention
Andrographolides
placebo
Sponsored by
About this trial
This is an interventional treatment trial for Primary Progressive Multiple Sclerosis
Eligibility Criteria
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
Sites / Locations
- Multiple Sclerosis Centre, Pontificia Universidad Catolica de ChileRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
andrographolides
sugar tablets
Arm Description
Coated tablets containing 140 mg andrographolides twice a day orally administered for a period of 24 months.
Coated tablets containing 140 mgs excipients twice a day orally administered for a period of 24 months.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Expanded Disability Status Scale (EDSS)
Delay in the disability capacity progression through the Expanded Disability Status Scale (EDSS) at 24 months compared to the baseline.
Paced Auditory Serial Addition Test (PASAT)
Delay in cognitive impairment by means of Paced Auditory Serial Addition Test (PASAT) at 24 months compared to the baseline.
Quality of life Multiple Sclerosis Impact Scale (MSIS 29)
Quality of life Multiple Sclerosis Impact Scale (MSIS 29) through parameters reported by the patients at 24 months compared to the baseline.
Treatment Satisfaction Questionnaire for Medication (TSQM)
Tolerability of andrographolide measured by the Treatment Satisfaction Questionnaire for Medication (TSQM) at 24 months.
Number of new T2 lesions
Number of new lesions T2 by MR at 24 months compared to the baseline.
New hypointense lesions in T1
Number of new hypointense lesions in T1 by MR at 24 months compared to the baseline.
Optical Coherence Tomography (OCT)
Delay in the retinal thinning measured by Optical Coherence Tomography (OCT) at 24 months compared to the baseline.
Record of adverse effects in daily symptoms and programmed interviews.
Safety of andrographolide at 24 months through the record of adverse effects in daily symptoms and programmed interviews.
Multiple Sclerosis Functional Composite (MSFC)
Delay in the disability capacity progression through the Multiple Sclerosis Functional Composite (MSFC) at 24 months compared to the baseline.
Symbol Digit Modalities Test (SDMT)
Delay in cognitive impairment by means of Symbol Digit Modalities Test (SDMT) at 24 months compared to the baseline.
Depression by Beck scale
Evaluate mood disorders by means of Beck scale at 24 months compared to the baseline.
Fatigue by Krupp scale
Evaluate fatigue by Krupp scale reported by the patients at 24 months compared to the baseline.
Number of new gadolinium enhancement lesions in T1 by MR
Number of new gadolinium enhancement lesions in T1 by MR at 24 months compared to the baseline.
Visual field
Change in visual field at 24 months compared to the baseline.
Volume of new T2 lesions
Volume of size in T2 by MR at 24 months compared to the baseline.
Full Information
NCT ID
NCT02273635
First Posted
October 3, 2014
Last Updated
October 24, 2014
Sponsor
Innobioscience SpA
Collaborators
Pontificia Universidad Catolica de Chile, University of Chile, Universidad Austral de Chile
1. Study Identification
Unique Protocol Identification Number
NCT02273635
Brief Title
Efficacy, Safety and Tolerability of Andrographolides Versus Placebo in Patients With Progressive Forms of MS
Official Title
Controlled, Randomized, Double-blind Clinical Trial, 24 Months Duration, to Compare the Efficacy, Safety and Tolerability of Andrographolide Versus Placebo in Patients With Progressive Forms of Multiple Sclerosis
Study Type
Interventional
2. Study Status
Record Verification Date
October 2014
Overall Recruitment Status
Unknown status
Study Start Date
September 2014 (undefined)
Primary Completion Date
November 2016 (Anticipated)
Study Completion Date
April 2017 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Innobioscience SpA
Collaborators
Pontificia Universidad Catolica de Chile, University of Chile, Universidad Austral de Chile
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
Detailed Description
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.
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Progressive Multiple Sclerosis, Multiple Sclerosis, Secondary Progressive
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
68 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
andrographolides
Arm Type
Experimental
Arm Description
Coated tablets containing 140 mg andrographolides twice a day orally administered for a period of 24 months.
Arm Title
sugar tablets
Arm Type
Placebo Comparator
Arm Description
Coated tablets containing 140 mgs excipients twice a day orally administered for a period of 24 months.
Intervention Type
Drug
Intervention Name(s)
Andrographolides
Other Intervention Name(s)
andrographolide, neoandrographolide, deoxyandrographolide, IB-MS 14
Intervention Description
140 mg andrographolides coated tablets twice a day orally administered for 24 months.
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
140 mg excipients coated tablets twice a day orally administered for 24 months
Primary Outcome Measure Information:
Title
Brain atrophy in patients with progressive forms of MS
Description
Retarding the progression of brain atrophy as measured by MR quantified by the percentage of change in volume size utilizing SIENA.
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Expanded Disability Status Scale (EDSS)
Description
Delay in the disability capacity progression through the Expanded Disability Status Scale (EDSS) at 24 months compared to the baseline.
Time Frame
24 months
Title
Paced Auditory Serial Addition Test (PASAT)
Description
Delay in cognitive impairment by means of Paced Auditory Serial Addition Test (PASAT) at 24 months compared to the baseline.
Time Frame
24 months
Title
Quality of life Multiple Sclerosis Impact Scale (MSIS 29)
Description
Quality of life Multiple Sclerosis Impact Scale (MSIS 29) through parameters reported by the patients at 24 months compared to the baseline.
Time Frame
24 months
Title
Treatment Satisfaction Questionnaire for Medication (TSQM)
Description
Tolerability of andrographolide measured by the Treatment Satisfaction Questionnaire for Medication (TSQM) at 24 months.
Time Frame
24 months
Title
Number of new T2 lesions
Description
Number of new lesions T2 by MR at 24 months compared to the baseline.
Time Frame
24 months
Title
New hypointense lesions in T1
Description
Number of new hypointense lesions in T1 by MR at 24 months compared to the baseline.
Time Frame
24 months
Title
Optical Coherence Tomography (OCT)
Description
Delay in the retinal thinning measured by Optical Coherence Tomography (OCT) at 24 months compared to the baseline.
Time Frame
24 months
Title
Record of adverse effects in daily symptoms and programmed interviews.
Description
Safety of andrographolide at 24 months through the record of adverse effects in daily symptoms and programmed interviews.
Time Frame
24 months
Title
Multiple Sclerosis Functional Composite (MSFC)
Description
Delay in the disability capacity progression through the Multiple Sclerosis Functional Composite (MSFC) at 24 months compared to the baseline.
Time Frame
24 months
Title
Symbol Digit Modalities Test (SDMT)
Description
Delay in cognitive impairment by means of Symbol Digit Modalities Test (SDMT) at 24 months compared to the baseline.
Time Frame
24 months
Title
Depression by Beck scale
Description
Evaluate mood disorders by means of Beck scale at 24 months compared to the baseline.
Time Frame
24 months
Title
Fatigue by Krupp scale
Description
Evaluate fatigue by Krupp scale reported by the patients at 24 months compared to the baseline.
Time Frame
24 months
Title
Number of new gadolinium enhancement lesions in T1 by MR
Description
Number of new gadolinium enhancement lesions in T1 by MR at 24 months compared to the baseline.
Time Frame
24 months
Title
Visual field
Description
Change in visual field at 24 months compared to the baseline.
Time Frame
24 months
Title
Volume of new T2 lesions
Description
Volume of size in T2 by MR at 24 months compared to the baseline.
Time Frame
24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Claudia A Carcamo, MD, PhD
Phone
+56223546885
Email
ccarcamo@med.puc.cl
First Name & Middle Initial & Last Name or Official Title & Degree
Ethel L Ciampi, MD
Phone
+56223546885
Email
anticsnap@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Juan L Hancke, DVM, PhD
Organizational Affiliation
Universidad Austral de Chile
Official's Role
Study Director
Facility Information:
Facility Name
Multiple Sclerosis Centre, Pontificia Universidad Catolica de Chile
City
Santiago
State/Province
Metropolitana
ZIP/Postal Code
8330033
Country
Chile
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Claudia A Carcamo, MD, PhD.
Phone
56 2 3546885
Email
ccarcamo@med.puc.cl
First Name & Middle Initial & Last Name & Degree
Ana C Reyes, Nurse
Phone
56 2 3546885
Email
acreyes@med.puc.cl
12. IPD Sharing Statement
Citations:
PubMed Identifier
15331658
Citation
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Results Reference
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PubMed Identifier
16597709
Citation
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.
Results Reference
background
PubMed Identifier
19408036
Citation
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.
Results Reference
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PubMed Identifier
24655808
Citation
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.
Results Reference
background
PubMed Identifier
19038244
Citation
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.
Results Reference
background
PubMed Identifier
15931581
Citation
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.
Results Reference
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PubMed Identifier
15678086
Citation
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.
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Citation
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.
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PubMed Identifier
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Results Reference
derived
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Efficacy, Safety and Tolerability of Andrographolides Versus Placebo in Patients With Progressive Forms of MS
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