| CTRI Number |
CTRI/2019/10/021540 [Registered on: 07/10/2019] Trial Registered Prospectively |
| Last Modified On: |
28/10/2024 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Nutraceutical |
| Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
Public Title of Study
Modification(s)
|
A study to evaluate efficacy and safety of Orally Administered Extract of Orthosiphon stamineus (Nuvastaticâ„¢ - C5OSEW5050ESA) for 12 months in Patients With Non-proliferative Diabetic Retinopathy Without Center-involved Diabetic Macular Edema. |
Scientific Title of Study
Modification(s)
|
A Randomized, Double-masked, Placebo-controlled phase 1b/2a study to evaluate Clinical efficacy and safety of Orally Administered Proprietary Extract of Orthosiphon stamineus (Nuvastaticâ„¢ - C5OSEW5050ESA) for 12 months treatment Period in Patients With Non-proliferative Diabetic Retinopathy Without Center-involved Diabetic Macular Edema. |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| BIAG-CSP-032 version1.0 dated 06-09-2019 |
Protocol Number |
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Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Modification(s)
|
| Name |
DR RAJESH PAREKH |
| Designation |
Consultant - Opthalmologist |
| Affiliation |
Consultant -SANJEEVANI NETHRALAYA & MEDICAL RESEARCH CENTER |
| Address |
SANJEEVANI NETHRALAYA & MEDICAL RESEARCH CENTER, 141, BHAGWAN MAHAVEER (INFANTRY) ROAD, OPPOSITE THE HINDU,BENGALURU – 560001.
Bangalore
KARNATAKA
560001.
India |
| Phone |
9945544744 |
| Fax |
|
| Email |
vision6by6@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Shalini Dayananda |
| Designation |
General Manager |
| Affiliation |
Bio Agile Therapeutics Pvt. Ltd |
| Address |
Bio Agile Therapeutics Pvt.Ltd. #2/5, Dahlia Building, 3rd floor, 80 Feet Road, RMV 2nd Stage, Bangalore, INDIA
Bangalore
KARNATAKA
560094
India |
| Phone |
08043754520 |
| Fax |
|
| Email |
pm@bioagiletherapeutics.com |
|
Details of Contact Person
Public Query
|
| Name |
Divya C |
| Designation |
Director |
| Affiliation |
Bio Agile Therapeutics Pvt. Ltd |
| Address |
Bio Agile Therapeutics Pvt.Ltd. #2/5, Dahlia Building, 3rd floor, 80 Feet Road, RMV 2nd Stage, Bangalore, INDIA
Bangalore
KARNATAKA
560094
India |
| Phone |
9538961761 |
| Fax |
|
| Email |
divya@bioagiletherapeutics.com |
|
|
Source of Monetary or Material Support
|
| Natureceuticals Sdn Bhd, A1-1, Lot 5, Persiaran 2/1, Kedah Halal Park, Kawasan Perindustrian Sungai Petani, 08000 Sungai Petani, Kedah, Penang, Malaysia. |
|
|
Primary Sponsor
|
| Name |
Natureceuticals Sdn Bhd |
| Address |
A1-1, Lot 5, 08000 Sungai Petani, Kedah, Penang, Malaysia. |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
|
Details of Secondary Sponsor
|
|
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Countries of Recruitment
|
India |
Sites of Study
Modification(s)
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| DR RAJESH PAREKH |
SANJEEVANI NETHRALAYA & MEDICAL RESEARCH CENTER |
SANJEEVANI NETHRALAYA & MEDICAL RESEARCH CENTER, 141, BHAGWAN MAHAVEER (INFANTRY) ROAD, OPPOSITE THE HINDU,BENGALURU – 560001.
Bangalore
KARNATAKA |
9945544744
vision6by6@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| ACE Ethics Committee |
Approved |
|
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Regulatory Clearance Status from DCGI
|
|
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Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: H36||Retinal disorders in diseases classified elsewhere, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Nuvastaticâ„¢ (containing 1000 mg of standardized extract of O. stamineus) |
will be given orally, three times per day for 12 months. |
| Comparator Agent |
NuvastaticTM (without active) |
given orally, three times per day for 12 months.
If patient progress to PDR or DME, laser photocoagulation will be prescribed |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
65.00 Year(s) |
| Gender |
Both |
| Details |
Type-2 Diabetes mellius (NIDDM) patients of both genders aged 18–65 years.
Able and willing to provide written informed consent.
Documented diagnosis of Type 2 diabetes mellitus a glycosylated hemoglobin A1c (HbA1c) of less than or equal to 12 at screening.
Patients preferably on oral medications for DM.
Meets specific ocular criteria for the study eye including but not limited to, the presence of non-proliferative diabetic retinopathy (NPDR) without center-involved diabetic macular edema (CI-DME) in the study eye at screening with NPDR level 47 or level 53, as determined by the central reading center (CRC) by using the DR severity scale (DRSS), for which treatment can be deferred for at least 4 weeks after Day 1 visit.
Media clarity, pupillary dilation, and subject cooperation sufficient to obtain adequate assessments. (Subject has early treatment diabetic retinopathy study (ETDRS) best corrected visual acuity (BCVA) letter score less than or equal to 73 (Snellen 20/40) and greater than or equal to 24 (Snellen 20/320) at screening visit).
Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial.
Study Eye Inclusion Criteria
Best corrected E-ETDRS visual acuity letter score ≥74 (i.e.20/32 or better) within 8 days of randomization.
On clinical exam, definite retinal thickening due to DME within 3000 μm of the center of the macula but not involving the central subfield.
Thickened non-central macular subfields on spectral domain OCT macular map that meet either of the following criteria:
a. At least two non-central macular subfields with OCT thickness above threshold (average normal + 2 SD) from DRCR.net approved spectral domain OCT machines- see below.
b. At least one non-central macular subfield with OCT thickness at least 15 μm above threshold (average normal + 2 SD) from DRCR.net approved spectral domain OCT machines—see DRCR.net procedures manual for threshold details.
Central subfield thickness less than 250 microns obtained by one of the DRCR.net approved spectral domain OCT machines
|
|
| ExclusionCriteria |
| Details |
• Insulin dependent Diabetes mellitus (IDDM or T1DM) patients.
• Any condition that would preclude participation in the study (e.g., unstable medical status including blood pressure, cardiovascular disease or glycemic control).
• History of myocardial infarction or other acute cardiac event.
• History of chronic renal failure requiring dialysis or kidney transplant.
• Prior participation in any clinical study.
• Treatment with any investigational study drug within 30 days of screening.
• Known allergy to study product.
• Treatment with specific prohibited medications or therapy beginning 4 weeks prior to screening and throughout the duration of the study.
• Subject with macular edema considered to be due to a cause other than DME, decrease in BCVA due to causes other than DME, significant macular ischemia, any other ocular disease that may cause substantial reduction in BCVA, active peri-ocular or ocular infection.
• Subject with an history of following within 3 months prior to Day 1: non-infectious uveitis, high myopia (-8 diopter or more correction), pars plana vitrectomy, any ocular surgery, prior IVT, subtenon, or periocular, non-sustained release, steroid therapy, uncontrolled glaucoma,
• History of systemic anti-VEGF or pro-VEGF treatment within 4 months prior to randomization.
• Any laboratory abnormalities at screening.
• Male subjects who are not surgically sterile and are not willing to practice a medically accepted method of birth control with their female partner of childbearing potential from screening through 30 days following completion of the study
• Female subjects of childbearing potential who are not willing to practice a medically accepted method of birth control with their non-surgically sterile male sexual partner from screening through 30 days following completion of the study
• Female subjects who are pregnant or lactating.
• Subject has media clarity, papillary constriction (i.e., senile miosis), or subject lacks cooperation that would interfere with any study procedures, evaluations or interpretation of data.
• Cataract surgery performed within 6 months prior to screening or planned during the trial; or any additional eye disease in the study eye that, in the opinion of the investigator, could compromise or alter visual acuity during the course of the study (e.g. vein occlusion, uncontrolled intraocular pressure (IOP) >24 mmHg on optimal medical treatment, glaucoma with visual field loss, uveitis or other ocular inflammatory disease, vitreomacular traction, monocular vision, history of ischemic optic neuropathy, or genetic disorders such as retinitis pigmentosa)
• Active center-involved DME (CI-DME) on clinical examination and Optical Coherence Tomography (OCT) central subfield thickness in the study eye above 300 μm as measured by Optovue OCT or above 320 μm as measured by Heidelberg OCT
• Anterior segment and vitreous abnormalities in the study eye that would compromise the adequate assessment of the best corrected visual acuity or an adequate examination of the posterior pole
|
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Pre-numbered or coded identical Containers |
|
Blinding/Masking
|
Participant and Investigator Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
Change in Central Subfield Retinal Thickness- Optical Coherence Tomography (OCT).
To compare the differences in protein biomarkers (VEGF and β-amyloid). |
baseline (day1), 6th Month and 12th Month. |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
The proportion of patients with any ocular adverse events (according to Common Terminology Criteria for Adverse Events (CTCAE) over the on treatment period (from baseline up to 12 months)
Change in Visual Acuity Letter Score from baseline over all Study Visits. |
baseline (day1), 6th Month and 12th Month. |
|
|
Target Sample Size
|
Total Sample Size="50"
Sample Size from India="50"
Final Enrollment numbers achieved (Total)= "70"
Final Enrollment numbers achieved (India)="70" |
|
Phase of Trial
|
Phase 1/ Phase 2 |
Date of First Enrollment (India)
Modification(s)
|
13/11/2020 |
| Date of Study Completion (India) |
10/08/2022 |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Date Missing |
|
Estimated Duration of Trial
|
Years="1"
Months="6"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Completed |
|
Publication Details
|
NIL |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
|
Brief Summary
|
Diabetic retinopathy
(DR) is a common complication of diabetes mellitus that leads to loss of vision
and blindness among working age adults. During progression of DR, patients
can develop diabetic macular edema (DME), which is characterized by the
thickening of the macula caused by the breakdown of the blood-retinal barrier and
consequent retinal vascular hyperpermeability. While there is no
curative treatment available for DME, laser photocoagulation represents an
effective treatment to preserve vision. However, this treatment modality is limited
by its inability to restore vision once it has been lost. The current
standard of care for DME includes intravitreal anti-vascular endothelial growth
factor (VEGF) therapeutics and corticosteroids. Thus, current
pharmacological treatments target single pathogenic processes with a narrow
therapeutic range and may cause adverse side effects leading to undesired
systemic effects. The presence of potential side effects and the significant
proportion of patients who do not respond to treatment suggest that there
remains a need for the development of improved therapies for DR and DME. As the bioactive principles of study product showed promising
results, the current clinical study has been conceptualized and designed to
assess the safety and efficacy of orally administered IP (1000
mg thrice daily ) for 12 months
treatment period in the Type -2 diabetic patients with non-proliferative
diabetic retinopathy without center-involved diabetic macular edema. The study population will be restricted to
non-insulin dependent diabetic patients as maximum as possible to avoid any
interference of the intensive insulin treatment . |