Multiple Sclerosis, Relapsing-RemittingPhase 1/2PCNS-EMNCT02280876
Efficacy Study of Andrographis Paniculata Purified Standardized Extract (ApE) in Patients With Multiple Sclerosis (MS)
A Phase 1/2 study testing 1 - Andrographis paniculata p/st extract and 2 - Excipients in people with Multiple Sclerosis, Relapsing-Remitting, run by Universidad Austral de Chile at 1 site in Chile.
Trial summary
To evaluate the efficacy of ApE coated tablets, on the relapse rate in a group of relapsing remitting multiple sclerosis (RRMS) patients, as compared to a placebo group in a period of 12 months. This study will also determine the safety and tolerability of the drug administered over interferon beta vs. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Multiple Sclerosis, Relapsing-Remitting
- What is being tested?
- 1 - Andrographis paniculata p/st extract and 2 - Excipients
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteChile
- Study dates
- Jan 2012to May 2015
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Patients diagnosed with MS according to McDonald scale
- Relapsing Remitting Forms of MS (subtypes of Lublin)
- Minor or less incapacity according to EDSS scale
- At least one relapse in the last 2 years
- Sign an informed consent
Who cannot join
- Primary and Secondary Progressive MS patients.
- Use of corticosteroids up to one month previous to enrollment
- Use of immunosuppressors up to one month previous to enrollment
- Use of drugs that induce hepatic metabolism
- Pregnancy, contraception, breast feeding.
- Psychiatric disorders
Show all 12Show fewer
- Systemic diseases
- Chronic renal failure
- Diabetes mellitus
- Cardiac failure
- Respiratory failure
- Cancer
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized, Comparative, Double Blind Controlled Phase II Clinical Trial, to Evaluate the Efficacy of ApE in Patients With Multiple Sclerosis (MS).
To evaluate the efficacy of ApE coated tablets, on the relapse rate in a group of relapsing remitting multiple sclerosis (RRMS) patients, as compared to a placebo group in a period of 12 months. This study will also determine the safety and tolerability of the drug administered over interferon beta vs. administration of a placebo formulation (also over interferon) during the evaluation period. Response will be assessed and measured by daily self patient recording, monthly clinical neurologist, and every three months serological and magnetic resonance parameters.
Place of Study: National study in Chile with one center at the Regional Hospital in the city of Valdivia, including 30 patients enrolled by their respective neurologists.
Read the detailed description
Introduction: Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system that predominantly affects young adults (1). Although its etiology has not yet been elucidated, evidence points to an autoimmune pathogenesis where it is thought that self-reactive and myelin-specific cluster of differentiation four and eight (CD4)and (CD8) T cells, play an important role by reacting and destroying the myelin sheath (2). No plasma biomarkers to determine disease activity by routine clinical measurements, the existence a pattern of pro-inflammatory cytokines has been described, with range increased Interferon (IFN), Tumoral Necrosis Factor alpha (TNFa) and Interleukin 12 (IL-12), as well as a decline in Interleukin10 (IL10) and Interleukin 4 (IL4) anti-inflammatory cytokines (3). To date, the most common treatment for MS is Interferon beta immunomodulation, although its cost / effectiveness has been questioned4.
Regardless of the progressive form and the existence of outbreaks, the fatigue symptom is one of the most frequent and disabling one in patients with MS. The proposed pathogenic mechanisms are multiple, although its exact pathophysiology is unknown. Also, there is still no treatment that has proven to be completely effective in stopping the progression of the disease (5). Description of the botanical drug to be used in this clinical research: The botanical drug to be used in this clinical research, is a phytopharmaceutical tablet made by Good Manufacturing Practices (GMP) containing a purified, standardized and patented extract of Andrographis paniculata Nees (Acanthaceae) {U.S. Patent: 8,084,495 B2; Date: Dec. 27, 2011} (ApE).
This is a medicinal annual plant, native to India and China whose active compounds are bitter diterpenoid lactones such as and especially 14-deoxyandrographolide, Neoandrographolide and specially Andrographolide, which has proven particularly effective in regulating the immune response (7, 9).
The cellular and molecular mechanisms responsible for the immunomodulatory and anti-inflammatory properties of Andrographolide, are for the most part still unknown. However, recent studies with in vitro and in vivo assays indicate that 10 micromol (µM) per liter inhibits Tumoral Necrosis Factor Beta (NF-kB). Specifically, Andrographolide at concentrations of 10 micromol (uM) per liter interferes with DNA binding of NF-kB (10), by reducing the expression of COX-2 in neutrophils induced with Formyl-Methionyl-Leucyl-Phenylalanine (fMLP) and Platelet Activating Factor (PAF). Moreover, Andrographolide reduces Interferon gamma (IFNg) and IL-2 production in Concanavalin A (Con A) induced T-cells, without affecting cell viability or inducing apoptosis, also diminishing thymocyte apoptosis induced by corticosteroids. Furthermore, Andrographolide and 14-deoxyandrographolide are capable of inhibiting extracellular signal-regulated kinases 1/2 (ERK1/2) phosphorylation in T cells and neutrophils, respectively (11, 12).
Security settings: Toxicity and Tolerance Analysis of acute and sub-chronic toxicity of ApE in rodents and pigs, using the basic component of ApE have been carried out in our laboratory at the Institute of Pharmacology and Toxicology, Universidad Austral de Chile, and according to the guidelines of Good Laboratory Practice (GLP) of the Food Administration Agency (FDA). Also, clinical phase I and II clinical studies have been performed, plus controlled daily treatment of 12 patients with different rheumatoid conditions and other 8 patients with Recurrent Remitting Multiple Sclerosis (RRMS) for more than five years. All these observations have proven a wide range of dosage safety without any detected toxic effects at therapeutic dose of 2 milligrams per kilogram of body weight.
Hypothesis: In experimental inflammatory and human autoimmune diseases, such as Rheumatoid arthritis and related conditions (17, 19), and also in animal models in which Experimental Autoimmune Encephalitis (EAE) is induced, we have recently shown that Andrographolide can significantly reduce the clinical symptoms and outcome of this diseases (6), for which we have now proposed this clinical study in RRMS.
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Being tested
- 1 - Andrographis paniculata p/st extract, 2 - Excipients
- Keywords
- MS, Demyelinating Autoimmune Diseases, CNS, Nervous System Diseases
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting, Nervous System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
1 - Andrographis paniculata p/st extractDrug
Also called Andrographolide, Verum formulation, Andrographis paniculata Extract ( ApE ), Paractin®
Andrographis paniculata Extract (ApE), Oral tablets 650 mg, with 170 mg. of andrographolides active principles, three times per day, during a total of 365 continuous days.
Other Names:
- ApE tablets, EUROMED Specific. Santiago Chile.
2 - ExcipientsDrug
Also called Placebo formulation
Placebo 650mg tabs, 2/day, 365 days continuously.
Other Names:
- Excipients tablets EUROMED Specific. Santiago Chile
| Study group | Role | What they receive |
|---|---|---|
| 1 - Andrographis paniculata p/st extract | Active comparator | 1 - Andrographis paniculata extract. Active comparator, consists of 15 adult patients with active Recurrent Remitting Multiple Sclerosis, randomly assigned, taking the active test product (Andrographis paniculata p/st extract, oral lozenges, one BID, for 12 months), in addition to base medication (Interferon). Receives: Drug: 1 - Andrographis paniculata p/st extract |
| 2 - Excipients | Placebo comparator | 2 - Excipients. Placebo comparator, consists of 15 adult patients with active Recurrent Remitting Multiple Sclerosis, randomly assigned, taking the placebo formulation (Only the excipients of the active test product, in oral lozenges of same shape, one BID, for 12 months), in addition to base medication (Interferon). Receives: Drug: 2 - Excipients |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical inflammatory (stamina) and disability score parameters (sensorial, neurosensitive, neuromotor and cognitive function) in patients with RRMS, treated with ApE and placebo administered over beta interferon.
Clinical parameters (stamina, sensorial, neurosensitive, neuromotor and cognitive function), will be measured by the Fatigue Severity Scale (FSS) and Expanded Disability Scale (EDSS) in patients with RRMS treated with ApE and placebo.
Measured: 12 months
Secondary outcomes (1)
Safety, tolerability and efficacy of ApE and placebo administered over beta interferon in RRMS treated patients (adverse symptoms, general clinical laboratory and comparative statistical parameters)
Patients dairy of possible adverse symptoms, general clinical laboratory and comparative statistical parameters
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2014 (estimated)
- Study startJan 2012
- Primary completionFeb 2015
- Study completionMay 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (18)Papers the sponsor has linked to this study.
- Other trials for Multiple Sclerosis, Relapsing-RemittingStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universidad Austral de Chile
- Sponsor type
- University, hospital or other
- Collaborators
- Comisión Nacional de Investigación Científica y Tecnológica, University of Chile
- Responsible party
- Principal investigator, Juan C. Bertoglio, MD, Universidad Austral de Chile
- Investigators
- Juan L. Hancke, PhD, Study director, Universidad Austral de Chile
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02280876
- Sponsor's protocol ID
- PaCRU-02/PCNS.EM/12
- Other IDs
- PCNS-EM
- Acronym
- PCNS-EM
- Status last verified
- Jan 2016
- First submitted
- 20 Oct 2014
- Last updated
- 23 Jun 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: All these trial results, will be submitted to publication in a major journal of the specialty, upon conclusion of data processing and evaluation.
Publications
Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple sclerosis. N Engl J Med. 2000 Sep 28;343(13):938-52. doi: 10.1056/NEJM200009283431307. No abstract available.
PubMed 11006371Wingerchuk DM, Lucchinetti CF, Noseworthy JH. Multiple sclerosis: current pathophysiological concepts. Lab Invest. 2001 Mar;81(3):263-81. doi: 10.1038/labinvest.3780235.
PubMed 11310820Galboiz Y, Miller A. Immunological indicators of disease activity and prognosis in multiple sclerosis. Curr Opin Neurol. 2002 Jun;15(3):233-7. doi: 10.1097/00019052-200206000-00002.
PubMed 12045718Phillips JT, Rice G, Frohman E, Vande Gaer L, Scott T, Haas J, Eggenberger E, Freedman MS, Stuart W, Cunha L, Jacobs L, Oger J, Arnold D, Murray TJ, DiBiase M, Jethwa V, Goelz S. A multicenter, open-label, phase II study of the immunogenicity and safety of a new prefilled syringe (liquid) formulation of Avonex in patients with multiple sclerosis. Clin Ther. 2004 Apr;26(4):511-21. doi: 10.1016/s0149-2918(04)90053-7.
PubMed 15189748Iruretagoyena 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.
PubMed 15331658Rajagopal S, Kumar RA, Deevi DS, Satyanarayana C, Rajagopalan R. Andrographolide, a potential cancer therapeutic agent isolated from Andrographis paniculata. J Exp Ther Oncol. 2003 May-Jun;3(3):147-58. doi: 10.1046/j.1359-4117.2003.01090.x.
PubMed 14641821Calabrese C, Berman SH, Babish JG, Ma X, Shinto L, Dorr M, Wells K, Wenner CA, Standish LJ. A phase I trial of andrographolide in HIV positive patients and normal volunteers. Phytother Res. 2000 Aug;14(5):333-8. doi: 10.1002/1099-1573(200008)14:53.0.co;2-d.
PubMed 10925397Hidalgo 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.
PubMed 15678086Burgos RA, Hidalgo MA, Monsalve J, LaBranche TP, Eyre P, Hancke JL. 14-deoxyandrographolide as a platelet activating factor antagonist in bovine neutrophils. Planta Med. 2005 Jul;71(7):604-8. doi: 10.1055/s-2005-871264.
PubMed 16041644Burgos 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.
PubMed 15931581Coon JT, Ernst E. Andrographis paniculata in the treatment of upper respiratory tract infections: a systematic review of safety and efficacy. Planta Med. 2004 Apr;70(4):293-8. doi: 10.1055/s-2004-818938.
PubMed 15095142Thamlikitkul V, Dechatiwongse T, Theerapong S, Chantrakul C, Boonroj P, Punkrut W, Ekpalakorn W, Boontaeng N, Taechaiya S, Petcharoen S, et al. Efficacy of Andrographis paniculata, Nees for pharyngotonsillitis in adults. J Med Assoc Thai. 1991 Oct;74(10):437-42.
PubMed 1797953Caceres DD, Hancke JL, Burgos RA, Wikman GK. Prevention of common colds with Andrographis paniculata dried extract. A Pilot double blind trial. Phytomedicine. 1997 Jun;4(2):101-4. doi: 10.1016/S0944-7113(97)80051-7.
PubMed 23195395Cabrera 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.
PubMed 24655808Caceres DD, Hancke JL, Burgos RA, Sandberg F, Wikman GK. Use of visual analogue scale measurements (VAS) to asses the effectiveness of standardized Andrographis paniculata extract SHA-10 in reducing the symptoms of common cold. A randomized double blind-placebo study. Phytomedicine. 1999 Oct;6(4):217-23. doi: 10.1016/S0944-7113(99)80012-9.
PubMed 10589439
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Comparative, Double Blind Controlled Phase II Clinical Trial, to Evaluate the Efficacy of ApE in Patients With Multiple Sclerosis (MS).
- ClinicalTrials.gov ID
- NCT02280876
- Acronym / sponsor ID
- PCNS-EM / PaCRU-02/PCNS.EM/12
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Keywords
- MS, Demyelinating Autoimmune Diseases, CNS, Nervous System Diseases
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Universidad Austral de ChileUniversity, hospital or other
- Collaborators
- Comisión Nacional de Investigación Científica y Tecnológica, University of Chile
- Study start
- Jan 2012
- Primary completion
- Feb 2015 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 3 Nov 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate the efficacy of ApE coated tablets, on the relapse rate in a group of relapsing remitting multiple sclerosis (RRMS) patients, as compared to a placebo group in a period of 12 months. This study will also determine the safety and tolerability of the drug administered over interferon beta vs. administration of a placebo formulation (also over interferon) during the evaluation period. Response will be assessed and measured by daily self patient recording, monthly clinical neurologist, and every three months serological and magnetic resonance parameters.
Place of Study: National study in Chile with one center at the Regional Hospital in the city of Valdivia, including 30 patients enrolled by their respective neurologists.
Detailed description
Introduction: Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system that predominantly affects young adults (1). Although its etiology has not yet been elucidated, evidence points to an autoimmune pathogenesis where it is thought that self-reactive and myelin-specific cluster of differentiation four and eight (CD4)and (CD8) T cells, play an important role by reacting and destroying the myelin sheath (2). No plasma biomarkers to determine disease activity by routine clinical measurements, the existence a pattern of pro-inflammatory cytokines has been described, with range increased Interferon (IFN), Tumoral Necrosis Factor alpha (TNFa) and Interleukin 12 (IL-12), as well as a decline in Interleukin10 (IL10) and Interleukin 4 (IL4) anti-inflammatory cytokines (3). To date, the most common treatment for MS is Interferon beta immunomodulation, although its cost / effectiveness has been questioned4.
Regardless of the progressive form and the existence of outbreaks, the fatigue symptom is one of the most frequent and disabling one in patients with MS. The proposed pathogenic mechanisms are multiple, although its exact pathophysiology is unknown. Also, there is still no treatment that has proven to be completely effective in stopping the progression of the disease (5). Description of the botanical drug to be used in this clinical research: The botanical drug to be used in this clinical research, is a phytopharmaceutical tablet made by Good Manufacturing Practices (GMP) containing a purified, standardized and patented extract of Andrographis paniculata Nees (Acanthaceae) {U.S. Patent: 8,084,495 B2; Date: Dec. 27, 2011} (ApE).
This is a medicinal annual plant, native to India and China whose active compounds are bitter diterpenoid lactones such as and especially 14-deoxyandrographolide, Neoandrographolide and specially Andrographolide, which has proven particularly effective in regulating the immune response (7, 9).
The cellular and molecular mechanisms responsible for the immunomodulatory and anti-inflammatory properties of Andrographolide, are for the most part still unknown. However, recent studies with in vitro and in vivo assays indicate that 10 micromol (µM) per liter inhibits Tumoral Necrosis Factor Beta (NF-kB). Specifically, Andrographolide at concentrations of 10 micromol (uM) per liter interferes with DNA binding of NF-kB (10), by reducing the expression of COX-2 in neutrophils induced with Formyl-Methionyl-Leucyl-Phenylalanine (fMLP) and Platelet Activating Factor (PAF). Moreover, Andrographolide reduces Interferon gamma (IFNg) and IL-2 production in Concanavalin A (Con A) induced T-cells, without affecting cell viability or inducing apoptosis, also diminishing thymocyte apoptosis induced by corticosteroids. Furthermore, Andrographolide and 14-deoxyandrographolide are capable of inhibiting extracellular signal-regulated kinases 1/2 (ERK1/2) phosphorylation in T cells and neutrophils, respectively (11, 12).
Security settings: Toxicity and Tolerance Analysis of acute and sub-chronic toxicity of ApE in rodents and pigs, using the basic component of ApE have been carried out in our laboratory at the Institute of Pharmacology and Toxicology, Universidad Austral de Chile, and according to the guidelines of Good Laboratory Practice (GLP) of the Food Administration Agency (FDA). Also, clinical phase I and II clinical studies have been performed, plus controlled daily treatment of 12 patients with different rheumatoid conditions and other 8 patients with Recurrent Remitting Multiple Sclerosis (RRMS) for more than five years. All these observations have proven a wide range of dosage safety without any detected toxic effects at therapeutic dose of 2 milligrams per kilogram of body weight.
Hypothesis: In experimental inflammatory and human autoimmune diseases, such as Rheumatoid arthritis and related conditions (17, 19), and also in animal models in which Experimental Autoimmune Encephalitis (EAE) is induced, we have recently shown that Andrographolide can significantly reduce the clinical symptoms and outcome of this diseases (6), for which we have now proposed this clinical study in RRMS.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 - Andrographis paniculata p/st extract | Active comparator | Drug: 1 - Andrographis paniculata p/st extract1 - Andrographis paniculata extract. Active comparator, consists of 15 adult patients with active Recurrent Remitting Multiple Sclerosis, randomly assigned, taking the active test product (Andrographis paniculata p/st extract, oral lozenges, one BID, for 12 months), in addition to base medication (Interferon). |
| 2 - Excipients | Placebo comparator | Drug: 2 - Excipients2 - Excipients. Placebo comparator, consists of 15 adult patients with active Recurrent Remitting Multiple Sclerosis, randomly assigned, taking the placebo formulation (Only the excipients of the active test product, in oral lozenges of same shape, one BID, for 12 months), in addition to base medication (Interferon). |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Patients diagnosed with MS according to McDonald scale
- Relapsing Remitting Forms of MS (subtypes of Lublin)
- Minor or less incapacity according to EDSS scale
- At least one relapse in the last 2 years
- Sign an informed consent
Key exclusion criteria (12 listed)
- Primary and Secondary Progressive MS patients.
- Use of corticosteroids up to one month previous to enrollment
- Use of immunosuppressors up to one month previous to enrollment
- Use of drugs that induce hepatic metabolism
- Pregnancy, contraception, breast feeding.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 1 - Andrographis paniculata p/st extractAlso: Andrographolide, Verum formulation, Andrographis paniculata Extract ( ApE ), Paractin®Andrographis paniculata Extract (ApE), Oral tablets 650 mg, with 170 mg. of andrographolides active principles, three times per day, during a total of 365 continuous days. Other Names: • ApE tablets, EUROMED Specific. Santiago Chile. | Drug | 1 - Andrographis paniculata p/st extract |
| 2 - ExcipientsAlso: Placebo formulationPlacebo 650mg tabs, 2/day, 365 days continuously. Other Names: • Excipients tablets EUROMED Specific. Santiago Chile | Drug | 2 - Excipients |
Primary outcome
Clinical inflammatory (stamina) and disability score parameters (sensorial, neurosensitive, neuromotor and cognitive function) in patients with RRMS, treated with ApE and placebo administered over beta interferon.
Time frame: 12 months
Clinical parameters (stamina, sensorial, neurosensitive, neuromotor and cognitive function), will be measured by the Fatigue Severity Scale (FSS) and Expanded Disability Scale (EDSS) in patients with RRMS treated with ApE and placebo.
1 secondary outcome
Safety, tolerability and efficacy of ApE and placebo administered over beta interferon in RRMS treated patients (adverse symptoms, general clinical laboratory and comparative statistical parameters)
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2016.
- Background: PubMed 11006371Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple sclerosis. N Engl J Med. 2000 Sep 28;343(13):938-52. doi: 10.1056/NEJM200009283431307. No abstract available.
- Background: PubMed 11310820Wingerchuk DM, Lucchinetti CF, Noseworthy JH. Multiple sclerosis: current pathophysiological concepts. Lab Invest. 2001 Mar;81(3):263-81. doi: 10.1038/labinvest.3780235.
- Background: PubMed 12045718Galboiz Y, Miller A. Immunological indicators of disease activity and prognosis in multiple sclerosis. Curr Opin Neurol. 2002 Jun;15(3):233-7. doi: 10.1097/00019052-200206000-00002.
- Background: PubMed 15189748Phillips JT, Rice G, Frohman E, Vande Gaer L, Scott T, Haas J, Eggenberger E, Freedman MS, Stuart W, Cunha L, Jacobs L, Oger J, Arnold D, Murray TJ, DiBiase M, Jethwa V, Goelz S. A multicenter, open-label, phase II study of the immunogenicity and safety of a new prefilled syringe (liquid) formulation of Avonex in patients with multiple sclerosis. Clin Ther. 2004 Apr;26(4):511-21. doi: 10.1016/s0149-2918(04)90053-7.
- Background: PubMed 15331658Iruretagoyena 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.
- Background: PubMed 14641821Rajagopal S, Kumar RA, Deevi DS, Satyanarayana C, Rajagopalan R. Andrographolide, a potential cancer therapeutic agent isolated from Andrographis paniculata. J Exp Ther Oncol. 2003 May-Jun;3(3):147-58. doi: 10.1046/j.1359-4117.2003.01090.x.
- Background: PubMed 10925397Calabrese C, Berman SH, Babish JG, Ma X, Shinto L, Dorr M, Wells K, Wenner CA, Standish LJ. A phase I trial of andrographolide in HIV positive patients and normal volunteers. Phytother Res. 2000 Aug;14(5):333-8. doi: 10.1002/1099-1573(200008)14:53.0.co;2-d.
- Background: PubMed 15678086Hidalgo 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.
- Background: PubMed 16041644Burgos RA, Hidalgo MA, Monsalve J, LaBranche TP, Eyre P, Hancke JL. 14-deoxyandrographolide as a platelet activating factor antagonist in bovine neutrophils. Planta Med. 2005 Jul;71(7):604-8. doi: 10.1055/s-2005-871264.
- Background: PubMed 15931581Burgos 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.
- Background: PubMed 15095142Coon JT, Ernst E. Andrographis paniculata in the treatment of upper respiratory tract infections: a systematic review of safety and efficacy. Planta Med. 2004 Apr;70(4):293-8. doi: 10.1055/s-2004-818938.
- Background: PubMed 1797953Thamlikitkul V, Dechatiwongse T, Theerapong S, Chantrakul C, Boonroj P, Punkrut W, Ekpalakorn W, Boontaeng N, Taechaiya S, Petcharoen S, et al. Efficacy of Andrographis paniculata, Nees for pharyngotonsillitis in adults. J Med Assoc Thai. 1991 Oct;74(10):437-42.
- Miller, Aaron E.; Coyle, Patricia K. CLINICAL FEATURES OF MULTIPLE SCLEROSIS. CONTINUUM: Lifelong Learning in Neurology. December 2004 - Volume 10 - Issue 6, Multiple Sclerosis - pp 38-73. doi: 10.1212/01.CON.0000293634.15851.7dLink provided by the sponsor.
- María A. Hidalgo, Juan L. Hancke, Juan C. Bertoglio and Rafael A. Burgos. Andrographolide, a New Potential Drug for the Long Term Treatment of Rheumatoid Arthritis Disease. Innovative Rheumatology. International standard book (ISBN) 978-953-51-0916-7Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. All these trial results, will be submitted to publication in a major journal of the specialty, upon conclusion of data processing and evaluation.
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Recruiting
Wearable Focal Vibration Therapy on Upper Extremity Function of People With Multiple Sclerosis: A Pilot Study
Multiple Sclerosis (MS) - Relapsing-remitting, Upper Extremity Dysfunction
Not yet recruiting
Treatment of Memory Retrieval Impairments in MS With HDtDCS to the LIFG in a Placebo Controlled Trial
Multiple Sclerosis, Relapsing-remitting Multiple Sclerosis (RRMS)
Recruiting
Monthly Monitoring of Plasma NfL in Treated Relapsing-remitting Multiple Sclerosis to Detect Persistent Infraclinical Disease Activity
Multiple Sclerosis (MS) - Relapsing-remitting
Active, not recruitingPhase 4
Safety and Efficacy Study of Fingolimod in Taiwanese Adults (≥ 20years) With Relapsing Remitting Multiple Sclerosis
Multiple Sclerosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Juan L. Hancke, PhD study director
Universidad Austral de Chile
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing 1 - Andrographis paniculata p/st extract and 2 - Excipients in people with Multiple Sclerosis, Relapsing-Remitting, run by Universidad Austral de Chile at 1 site in Chile.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Chile. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical inflammatory (stamina) and disability score parameters (sensorial, neurosensitive, neuromotor and cognitive function) in patients with RRMS, treated with ApE and placebo administered over beta interferon. (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02280876, which also lists 18 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2016.