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

Study Overview
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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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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.

Official Title
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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

Conditions
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Primary Progressive Multiple Sclerosis, Multiple Sclerosis, Secondary Progressive

Intervention / Treatment
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* Drug: Andrographolides
* Drug: placebo


Participation Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: andrographolides<br>Coated tablets containing 140 mg andrographolides twice a day orally administered for a period of 24 months. | Drug: Andrographolides<br>* 140 mg andrographolides coated tablets twice a day orally administered for 24 months.<br>* Other names: IB-MS 14;|
| Placebo Comparator: sugar tablets<br>Coated tablets containing 140 mgs excipients twice a day orally administered for a period of 24 months. | Drug: placebo<br>* 140 mg excipients coated tablets twice a day orally administered for 24 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 24 months | 
| 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. | 24 months | 
| 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. | 24 months | 
| Treatment Satisfaction Questionnaire for Medication (TSQM) | Tolerability of andrographolide measured by the Treatment Satisfaction Questionnaire for Medication (TSQM) at 24 months. | 24 months | 
| Number of new T2 lesions | Number of new lesions T2 by MR at 24 months compared to the baseline. | 24 months | 
| New hypointense lesions in T1 | Number of new hypointense lesions in T1 by MR at 24 months compared to the baseline. | 24 months | 
| Optical Coherence Tomography (OCT) | Delay in the retinal thinning measured by Optical Coherence Tomography (OCT) at 24 months compared to the baseline. | 24 months | 
| 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. | 24 months | 
| 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. | 24 months | 
| Symbol Digit Modalities Test (SDMT) | Delay in cognitive impairment by means of Symbol Digit Modalities Test (SDMT) at 24 months compared to the baseline. | 24 months | 
| Depression by Beck scale | Evaluate mood disorders by means of Beck scale at 24 months compared to the baseline. | 24 months | 
| Fatigue by Krupp scale | Evaluate fatigue by Krupp scale reported by the patients at 24 months compared to the baseline. | 24 months | 
| 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. | 24 months | 
| Visual field | Change in visual field at 24 months compared to the baseline. | 24 months | 
| Volume of new T2 lesions | Volume of size in T2 by MR at 24 months compared to the baseline. | 24 months |