Not Yet RecruitingPhase 2ACTRN12621001268831

The effect of tocotrienol-rich vitamin E (Tocovid Suprabio) compared to tocopherol on diabetic microvascular complications: A double-blinded placebo controlled, multicentre clinical trial

The Effect of Lower-dose 100mg and 200mg Tocotrienol-rich Vitamin E (Tocovid Suprabio®) and 200IU Alpha-Tocopherol on Diabetic Microvascular Complications in Patients with Diabetes

Sponsor

Monash University Malaysia

Enrollment

200 participants

Start Date

Nov 1, 2022

Study Type

Interventional

Conditions

Diabetes Mellitus Diabetic Retinopathy Diabetic Nephropathy Diabetic Neuropathy

Summary

The overarching aim of the research is to establish the potential mechanisms of action(s) of increasing doses tocotrienol-rich Vitamin E on diabetes and its diabetes microvascular complications, namely nephropathy, retinopathy and neuropathy. In this study, we aim to establish the potential renal-, retinal- and/or neuro-protective role(s) of increasing doses of tocotrienol-rich Vitamin E by measuring the renal, retinal and nerve parameters respectively. In addition, we focus on investigating the mechanisms by which tocotrienol-rich Vitamin E improves nerve function, protects the retina and gives renal protection. We will also look into the superiority of tocotrienol-rich Vitamin E to natural alpha-tocopherol (200IU) in showing beneficial effects on the diabetic complications. This is a prospective, multi-centered, randomized, double-blinded, placebo-controlled study involving patients with type 2 diabetes mellitus with reasonable glycaemic control (HbA1c between 6.0 - 9.0%) and diabetic neuropathy as assessed by nerve conduction study. Subjects in interventional groups will receive one of the following treatments: 100mg of tocotrienol-rich Vitamin E, 200mg of tocotrienol-rich Vitamin E or 200IU of alpha-tocopherol once per day for 24 weeks. The control arm will receive matching placebo once per day for 24 weeks. All study subjects will be followed up at 2, 4, 8, 12, and 24 weeks throughout the double-blinded treatment period. Study subjects will be asked to return 3 months after treatment cessation to monitor for adverse events. The detail timeline of the study will be provided in the relevant section below. The improvement of the microvascular complications will be assessed by respective parameters as follows: (i) Nephropathy: UACR & eGFR (ii) Retinopathy: Intraretinal hemorrhages & macular edema by means of fundal photography (iii) Peripheral Neuropathy: Nerve conduction study parameters

Eligibility

Sex: Both males and femalesMin Age: 30 YearssMax Age: 75 Yearss

Inclusion Criteria11

Subject, or legal representative, has voluntarily signed and dated an Informed Consent Form.
Subject is 30-75 years of age at the initial Screening visit.
Subject has type 2 diabetes mellitus (T2DM) with stable glucose control (not more than 10% change in HbA1c levels over the last 2 months) and the HbA1c range should be within 6-9%.
If a subject has hypertension, he/she must have a stable blood pressure control for the past 2 months with not more than 10% change and the blood pressure (BP) range should be less than 145/90 mmHg.
Subject has at least one of the following symptoms of diabetic peripheral neuropathy:
(a) Reduction in nerve conduction velocity (defined by baseline conduction velocity less than 40m/s)
(b) Reduction in negative to peak (NP) and peak to peak (PP) amplitude
(c) Abnormality found in clinical assessment (Eg: pain, light, touch, temperature, position sense, vibration and reflexes)
Subject has either one of the following or both:
(a) Inactive diabetic retinopathy as assessed by retinal photography
(b) Mild to moderate nephropathy which is defined by urine albumin-to-creatinine ratio (UACR) of greater than 20 mg/g or eGFR between 30 to 60 ml/min/bsa (Stage 3 chronic kidney disease (CKD))

Exclusion Criteria16

Subject is pregnant during screening OR planning to be pregnant OR not on contraception
Subject has urine protein greater than150 g/L during screening
Subject has current urinary tract infection during screening (symptomatic or definitively
on urine dipstick: presence of pyuria, nitrites and red blood cells)
Subject has known non-diabetic kidney disease, such as kidney stones, etc.
Subject has a corrected visual acuity of less than 20/200
Subject with eye diseases such as media opacity, amblyopic and glaucoma
Subject on anti-epileptic or sedative medications
Subject has acute or severe chronic illness such as acute coronary syndrome, active
tuberculosis, and previous or current history of cancer, liver or inflammatory disease,
etc.
Subject is taking other water-soluble antioxidants for the past 2 weeks or fat-soluble
antioxidants for the past 1 month
Subject is a heavy smoker (equal to 20 sticks/day) or has stopped smoking for less than 1 month
Subject has elevated liver enzymes (serum ALT and/or serum AST greater than 3x the upper limit of normal)
Subject with severely deranged renal profile. (Stage 5 CKD; eGFR less than or equal to 15 ml/min/bsa)

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Interventions

Arm 1: 100mg tocotrienol-rich Vitamin E from palm oil Dose: 100mg once daily Duration: 24 weeks Mode of administration: Oral capsule Active ingredients: 1) d-Alpha Tocotrienol 30.76mg 2) d-Gamma

Arm 1: 100mg tocotrienol-rich Vitamin E from palm oil Dose: 100mg once daily Duration: 24 weeks Mode of administration: Oral capsule Active ingredients: 1) d-Alpha Tocotrienol 30.76mg 2) d-Gamma-Tocotrienol 56.40mg 3) d-Delta-Tocotrienol 12.84mg 4) d-Alpha-Tocopherol 45.80IU 5) Plant Squalene 25.64mg 6) Phytosterol Complex 10.24mg 7) Phytocarotenoid Complex 180.00ug Arm 2: 200mg tocotrienol-rich Vitamin E from palm oil Dose: 200mg once daily Duration: 24 weeks Mode of administration: Oral capsule Active ingredients: 1) d-Alpha-Tocotrienol 61.52mg 2) d-Gamma-Tocotrienol 112.80mg 3) d-Delta-Tocotrienol 25.68mg 4) d-Alpha-Tocopherol 91.60IU 5) Plant Squalene 51.28mg 6) Phytosterol Complex 20.48mg 7) Phytocarotenoid Complex 360.00ug Arm 3: Alpha-tocopherol Dose: 200IU once daily Duration: 24 weeks Mode of administration: Oral capsule Active ingredients: d-Alpha-Tocopherol 200IU Adherence will be assessed by counting the remaining capsules brought back by the participants during the follow-up visits. In addition, the plasma Vitamin E levels will be measured to assess adherence of the participants.