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

Phase 1

• Conditions: Primary Progressive Multiple Sclerosis; Multiple Sclerosis, Secondary Progressive
• Interventions: Drug: placebo; Drug: Andrographolides

• Registration Number: NCT02273635
• Lead Sponsor: Innobioscience SpA

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

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.

Study Timeline

• Study Start: 2014-09
• Status Verified: 2014-10
• Study First Submitted: 2014-10-03
• Study First Submitted QC: 2014-10-23
• Study First Posted: 2014-10-24
• Last Update Submitted: 2014-10-24
• Last Update Posted: 2014-10-27
• Primary Completion: 2016-11
• Study Completion: 2017-04

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 68

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
sugar tablets	placebo	Coated tablets containing 140 mgs excipients twice a day orally administered for a period of 24 months.
andrographolides	Andrographolides	Coated tablets containing 140 mg andrographolides twice a day orally administered for a period of 24 months.

Primary Outcome Measures

Name	Time	Method
Brain atrophy in patients with progressive forms of MS	24 months	Retarding the progression of brain atrophy as measured by MR quantified by the percentage of change in volume size utilizing SIENA.

Secondary Outcome Measures

Name	Time	Method
Number of new T2 lesions	24 months	Number of new lesions T2 by MR at 24 months compared to the baseline.
Fatigue by Krupp scale	24 months	Evaluate fatigue by Krupp scale reported by the patients at 24 months compared to the baseline.
Expanded Disability Status Scale (EDSS)	24 months	Delay in the disability capacity progression through the Expanded Disability Status Scale (EDSS) at 24 months compared to the baseline.
Multiple Sclerosis Functional Composite (MSFC)	24 months	Delay in the disability capacity progression through the Multiple Sclerosis Functional Composite (MSFC) at 24 months compared to the baseline.
New hypointense lesions in T1	24 months	Number of new hypointense lesions in T1 by MR at 24 months compared to the baseline.
Record of adverse effects in daily symptoms and programmed interviews.	24 months	Safety of andrographolide at 24 months through the record of adverse effects in daily symptoms and programmed interviews.
Depression by Beck scale	24 months	Evaluate mood disorders by means of Beck scale at 24 months compared to the baseline.
Visual field	24 months	Change in visual field at 24 months compared to the baseline.
Paced Auditory Serial Addition Test (PASAT)	24 months	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)	24 months	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)	24 months	Tolerability of andrographolide measured by the Treatment Satisfaction Questionnaire for Medication (TSQM) at 24 months.
Optical Coherence Tomography (OCT)	24 months	Delay in the retinal thinning measured by Optical Coherence Tomography (OCT) at 24 months compared to the baseline.
Number of new gadolinium enhancement lesions in T1 by MR	24 months	Number of new gadolinium enhancement lesions in T1 by MR at 24 months compared to the baseline.
Symbol Digit Modalities Test (SDMT)	24 months	Delay in cognitive impairment by means of Symbol Digit Modalities Test (SDMT) at 24 months compared to the baseline.
Volume of new T2 lesions	24 months	Volume of size in T2 by MR at 24 months compared to the baseline.

Trial Locations

Locations (1)

Multiple Sclerosis Centre, Pontificia Universidad Catolica de Chile; 🇨🇱 Santiago, Metropolitana, Chile