Efficacy of A Non-Invasive Botulinum Toxin Microneedle Pad for the Treatment of Secondary Raynaud's Phenomenon and Digital Ulcers in Systemic Sclerosis: A Randomized Placebo-Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 72
- 主要终点
- Change from baseline in distal digit temperature at 4 Weeks
研究概览
简要总结
Raynaud's Phenomenon (RP), a vasospastic disorder causing digital ischemia and potential tissue necrosis, is effectively treated with Botulinum Toxin Type A (BTX-A) in refractory cases. However, standard administration requires painful, invasive injections that risk infection and localized muscle weakness. To address these limitations, this randomized, placebo-controlled, parallel-group study evaluates a microneedle delivery system designed to reach the dermis while avoiding systemic circulation. By penetrating 70-80% of their height, these microneedles aim to improve hand function and symptom scores for adult systemic sclerosis patients through a more comfortable, portable, and less invasive method that increases delivery surface area while minimizing pain.
详细描述
Background
Botulinum toxin-A (BTX-A) has demonstrated effectiveness in treating Raynaud's phenomenon in systemic sclerosis (RP-SSc) by improving hand function and condition scores. The current standard of care requires BTX-A to be administered via multiple, painful invasive injections, which carry recognized risks including local infection at injection sites and transient localized intrinsic hand muscle weakness due to toxin diffusion. Microneedles are developed to reduce injection pain and provide a less invasive method than conventional injections. This study evaluates the efficacy and adverse reactions of a BTX-A microneedle pad compared with 2% topical isosorbide dinitrate (ISDN) cream for the treatment of RP-SSc. The microneedles are specifically designed to penetrate the epidermis and reach the dermis layer. This design facilitates localized drug delivery while ensuring the needle tips do not reach blood vessels, preventing the drug from entering systemic circulation. The microneedle array is engineered with an evaluated penetration depth of around 70-80% of its height. The targeted insertion sites for the microneedles are located on the lateral and slightly dorsal aspects of the proximal finger base.
Study Design and Treatment Arms
The trial is a randomized, placebo-controlled, parallel-group study.
Group A (Botox) receives a one-time BTX-A microneedle pad (10 units per pad) applied once on the affected hand plus topical placebo cream applied three times daily.
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
- Triple (Participant, Care Provider, Outcomes Assessor)
盲法说明
The placebo has been assigned for the controlled group.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •SSc patients aged between 18 and 70 years
- •Diagnosed according to ACR/EULAR 2013 classification criteria20
- •Having RP with/without DU on fingers or toes
- •Understand and able to read and write Thai language
- •Stable steroid, immunosuppressant, and vasodilator including CCB, PDE5i for at least 4 weeks before enrollment
排除标准
- •History of allergy or hypersensitivity to Botulinum toxin or ISDN
- •Overlap with other connective tissue diseases
- •Documented having peripheral arterial disease or vasculitis that affected vascular supply of fingers or toes
- •Current use of 2% ISDN cream for treatment of RP
- •Current use vasoconstrictor or medication that has vasoconstrictor effect such as ergotamine sulfate, beta-blocker
- •Pregnancy and lactating patients
- •Bedridden and confined to no self-care
- •Evidence of active malignant disease
- •Active infection or sepsis
- •Localized infection of hand
- •Impaired of intrinsic muscle hand function
- •Active smoker
- •Prior upper extremity vascular surgery, including surgical sympathectomy within 1 month before enrollment
研究组 & 干预措施
Intervention group
Group A: Botulinum toxin A with placebo cream
干预措施: Botulinum toxin A via microneedle (Drug)
Control group
Group B: Placebo botulinum A with isosorbide dinitrate cream
干预措施: Control (Normal saline) (Other)
结局指标
主要结局
Change from baseline in distal digit temperature at 4 Weeks
时间窗: Baseline and 4 weeks after treatment
The change in distal digit temperature is evaluated using an infrared thermometer from baseline to 4 weeks after treatment.
次要结局
- Change from baseline in Raynaud's Phenomenon pain severity score on the Visual Analogue Scale (VAS)(Baseline to 1 week, baseline to 4 weeks, and baseline to 12 weeks after treatment)
- Number of participants experiencing local adverse events at the application site(1 week, 4 weeks, and 12 weeks after treatment)
- Change from baseline in Raynaud's Condition Score (RCS)(Baseline to 1 week, baseline to 4 weeks, and baseline to 12 weeks after treatment)
- The progression of Raynaud's phenomenon (RP) to digital ulcer (DU)(1, 4, and 12 weeks)
- The progression of Raynaud's phenomenon (RP) to digital ulcer (DU)(1, 4 , and 12 weeks after treatment)
- The clinical benefit and safety of microneedle pad(1, 4, and 12 weeks)
- The clinical benefit and safety of microneedle pad(1, 4, and 12 weeks after treatment)
- The progression of Raynaud's phenomenon (RP) to digital ulcers (DUs)(1, 4 , and 12 weeks after treatment)
研究者
Chingching Foocharoen
Professor
Khon Kaen University