The Effect of Oral DLBS1033 as Adjuvant Therapy on Inflammatory Biomarkers, Neuroregeneration Biomarkers, and Disease Severity in Patients With Diabetic Polyneuropathy: A Randomized Controlled Trial (An Evaluation of Changes in TCNS, TNF-α, NGF, and Sensory Nerve Conduction Study of the Sural Nerve)
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 34
- 试验地点
- 1
- 主要终点
- Change in Toronto Clinical Neuropathy Score (TCNS)
研究概览
简要总结
This study aims to evaluate whether oral DLBS1033 can improve clinical symptoms and biological markers of nerve damage in adults with diabetic polyneuropathy. The trial enrolls patients with type 2 diabetes who show clinical signs of peripheral nerve injury.
Participants will receive either DLBS1033 as adjuvant therapy or standard therapy alone for 28 days. The study will compare changes in neuropathy severity (Toronto Clinical Neuropathy Score), inflammatory biomarkers (TNF-α), neuroregeneration biomarkers (Nerve Growth Factor), and sensory nerve conduction parameters of the sural nerve between the two groups. Blood tests, clinical assessments, and nerve conduction studies will be performed at baseline and follow-up visits. Participants will also report any symptoms or adverse events throughout the study.
详细描述
This study is a double-blind, randomized, placebo-controlled clinical trial conducted at RSUD Dr. Moewardi, Surakarta. Participants are adults aged 40-60 years with clinically diagnosed diabetic polyneuropathy and HbA1c levels between 7-10%. After screening and confirmation of eligibility, participants are randomized in a 1:1 ratio to receive either oral DLBS1033 (3 × 980 mg daily for 28 days) or placebo, in addition to standard DPN management. Randomization is performed by a third party using permuted block randomization via an online allocation system.
The study evaluates changes in:
- Inflammatory activity, measured by serum TNF-α
- Neuroregeneration, measured by serum NGF
- Clinical severity, assessed using the Toronto Clinical Neuropathy Score (TCNS)
- Electrophysiological function, assessed by sensory nerve conduction velocity and amplitude of the sural nerve These parameters are measured at baseline (Day 0) and after 28 days of treatment. A ±2-day window (Day 26-30) is permitted for follow-up assessments. Participants continue receiving their assigned intervention during this window.
Rationale DPN is driven by multiple interacting mechanisms, including oxidative stress, microvascular ischemia, and chronic low-grade inflammation. TNF-α is a key pro-inflammatory cytokine implicated in nerve injury, demyelination, and axonal degeneration. Elevated TNF-α levels correlate with DPN severity and may serve as a therapeutic target. Conversely, NGF is essential for the survival and regeneration of small-fiber and large-fiber neurons. Reduced NGF availability contributes to impaired nerve repair and progression of neuropathy. The protocol highlights that "NGF levels are significantly reduced in patients with diabetic neuropathy," and that restoring NGF may support nerve recovery.
DLBS1033 has demonstrated the ability to reduce TNF-α expression and enhance NGF production in preclinical models. It also improves microcirculation through fibrinolytic and antiplatelet effects, which may alleviate endoneurial ischemia-a major contributor to DPN. These combined mechanisms provide a strong biological rationale for evaluating DLBS1033 as an adjuvant therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Care Provider)
入排标准
- 年龄范围
- 40 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults aged 40-60 years diagnosed with diabetic polyneuropathy by a neurologist or neurology resident.
- •Patients with HbA1c levels between 7-10% within the past 30 days.
- •Willing to participate and able to sign the informed consent form.
排除标准
- •Pregnant, breastfeeding, or planning pregnancy.
- •History of other neurological diseases such as stroke, myelopathy, alcoholic neuropathy, or compressive radiculopathy.
- •Significant renal impairment (creatinine > 1.5× upper limit of normal), hepatic impairment (SGOT or SGPT > 3× upper limit of normal), or severe cardiac disease (NYHA class III-IV heart failure).
- •History of alcohol consumption for ≥ 5 consecutive years.
- •Heavy smoker (Brinkman Index > 600).
- •Known allergy or intolerance to DLBS
- •Autoimmune disease, malignancy, or acute and/or chronic inflammatory conditions other than diabetic polyneuropathy.
- •Participation in another interventional pharmacological clinical study within 30 days prior to screening.
- •Currently taking anti-inflammatory and/or antioxidant medications.
研究组 & 干预措施
Experimental: DLBS1033 + Standard Therapy
Participants receive oral DLBS1033 as adjuvant therapy in addition to standard therapy for diabetic polyneuropathy.
Intervention Drug: DLBS1033 Dose: 980 mg orally, three times daily Duration: 28 days Description: DLBS1033 contains lumbrokinase (Lumbricus low-molecular-weight proteins) with anti-inflammatory, fibrinolytic, and neuroregenerative activity.
Other Components: Standard therapy for diabetic polyneuropathy (per treating physician).
干预措施: DLBS1033 (Drug)
Experimental: DLBS1033 + Standard Therapy
Participants receive oral DLBS1033 as adjuvant therapy in addition to standard therapy for diabetic polyneuropathy.
Intervention Drug: DLBS1033 Dose: 980 mg orally, three times daily Duration: 28 days Description: DLBS1033 contains lumbrokinase (Lumbricus low-molecular-weight proteins) with anti-inflammatory, fibrinolytic, and neuroregenerative activity.
Other Components: Standard therapy for diabetic polyneuropathy (per treating physician).
干预措施: Placebo Comparator: Placebo + Standard Therapy (Drug)
Placebo Comparator: Placebo + Standard Therapy
Participants receive placebo capsules identical in appearance to DLBS1033, in addition to standard therapy.
Intervention Drug: Placebo Dose: Matching placebo, orally, three times daily Duration: 28 days Other Components: Standard therapy for diabetic polyneuropathy (per treating physician).
干预措施: DLBS1033 (Drug)
Placebo Comparator: Placebo + Standard Therapy
Participants receive placebo capsules identical in appearance to DLBS1033, in addition to standard therapy.
Intervention Drug: Placebo Dose: Matching placebo, orally, three times daily Duration: 28 days Other Components: Standard therapy for diabetic polyneuropathy (per treating physician).
干预措施: Placebo Comparator: Placebo + Standard Therapy (Drug)
结局指标
主要结局
Change in Toronto Clinical Neuropathy Score (TCNS)
时间窗: Baseline and Day 28
TCNS is a validated clinical scoring system that assesses neuropathy severity based on symptoms, sensory testing, and reflex examination, with the minimum value of 0 and maximum value of 19 points. A decrease in TCNS indicates improvement in neuropathy severity.
次要结局
- Change in Tumor Necrosis Factor-α (TNF-α) Level(Baseline and Day 28)
- Change in Nerve Growth Factor (NGF) Level(Baseline and Day 28)
- Change in Sensory Nerve Conduction Velocity of the Sural Nerve(Baseline and Day 28)
- Change in Sural Sensory Nerve Amplitude(Baseline and Day 28)
研究者
Krisandi Hartanto
MD
Universitas Sebelas Maret