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Efficacy of A Non-Invasive Botulinum Toxin Microneedle Pad for the Treatment of Secondary Raynaud's Phenomenon (Botox SSc-RP)

13 sierpnia 2026 zaktualizowane przez: Chingching Foocharoen, Khon Kaen University

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

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.

Przegląd badań

Status

Jeszcze nie rekrutacja

Warunki

Interwencja / Leczenie

Szczegółowy opis

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.

Group B (Nitrate) receives a placebo microneedle pad (normal saline) applied once plus 2% topical ISDN cream applied three times daily.

Drug Preparation and Administration

The investigational BTX-A product is supplied as a sterile, vacuum-dried powder in a single-use vial containing 100 Units, which is reconstituted with 0.9% sterile, preservative-free sodium chloride to achieve a concentration of 10 units/mL. The medication is divided and administered to both lateral sides of the digits, with 5 units (0.5 mL) administered per side.

The 2% ISDN topical emulsion is compounded by mixing the crushed equivalent of 400 sublingual tablets (5 mg per tablet) with 85 g of a semisolid hydrophilic base. The ISDN preparation is divided into 10 g units and assigned a 6-month expiration date when stored at temperatures between 2 and 8°C.

Study Procedures and Follow-up Schedule

Baseline evaluations include medical history, serological tests, demographic data, vital signs, physical examinations, clinical characteristics of SSc, concomitant medications, and comorbidities. Routine laboratory assessments include complete blood count, erythrocyte sedimentation rate, c-reactive protein, renal function, liver function, urinalysis, creatine kinase, thyroid function test, chest radiography, pulmonary function test, and echocardiography.

Follow-up evaluations occur at Week 1, Week 4, and Week 12 post-treatment to monitor vital signs, physical examinations, clinical characteristics of SSc, routine laboratory assessments, concomitant medications, drug compliance, and complications such as intrinsic hand muscle weakness.

Withdrawal, Rescue Therapy, and Termination CriteriaParticipants will be withdrawn from the study if they develop active systemic infection, localized infection at microneedle pad sites, serious adverse events relating to BTX-A (such as weakened hand grip or paresthesia), severe local allergic reactions, intolerable pain from microneedle application, inability to tolerate wearing the patch until full absorption, worsening Raynaud's phenomenon, new digital ulcers, gangrene, severe headache, need for hospitalization, undergo hand surgery during the study, or self-withdraw. Participants withdrawn due to severe Raynaud's phenomenon or increased digital ulcer size will receive rescue therapy with a systemic vasodilator. Participants requiring rescue medication will continue to be followed for the full 12-week study period, and their data will be included in the Intention-to-Treat (ITT) analysis in compliance with ICH-GCP E6 (R3).

The study will be terminated if the prevalence of serious adverse events (weakened hand grip, paresthesia) in the BTX-A microneedle pad group exceeds 20% (7 cases), or if 15% of enrolled participants (6 cases) experience intolerable pain from the pad, bleeding, or local infection.

Typ studiów

Interwencyjne

Zapisy (Szacowany)

72

Faza

  • Faza 3

Kontakty i lokalizacje

Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.

Kontakt w sprawie studiów

  • Nazwa: Chingching Foocharoen, MD
  • Numer telefonu: 66906784212
  • E-mail: fching@kku.ac.th

Kopia zapasowa kontaktu do badania

Kryteria uczestnictwa

Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.

Kryteria kwalifikacji

Wiek uprawniający do nauki

  • Dorosły
  • Starszy dorosły

Akceptuje zdrowych ochotników

Nie

Opis

Inclusion Criteria:

  1. SSc patients aged between 18 and 70 years
  2. Diagnosed according to ACR/EULAR 2013 classification criteria20
  3. Having RP with/without DU on fingers or toes
  4. Understand and able to read and write Thai language
  5. Stable steroid, immunosuppressant, and vasodilator including CCB, PDE5i for at least 4 weeks before enrollment

Exclusion Criteria:

  1. History of allergy or hypersensitivity to Botulinum toxin or ISDN
  2. Overlap with other connective tissue diseases
  3. Documented having peripheral arterial disease or vasculitis that affected vascular supply of fingers or toes
  4. Current use of 2% ISDN cream for treatment of RP
  5. Current use vasoconstrictor or medication that has vasoconstrictor effect such as ergotamine sulfate, beta-blocker
  6. Pregnancy and lactating patients
  7. Bedridden and confined to no self-care
  8. Evidence of active malignant disease
  9. Active infection or sepsis
  10. Localized infection of hand
  11. Impaired of intrinsic muscle hand function
  12. Active smoker
  13. Prior upper extremity vascular surgery, including surgical sympathectomy within 1 month before enrollment

Plan studiów

Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.

Jak projektuje się badanie?

Szczegóły projektu

  • Główny cel: Leczenie
  • Przydział: Randomizowane
  • Model interwencyjny: Przydział równoległy
  • Maskowanie: Potroić

Broń i interwencje

Grupa uczestników / Arm
Interwencja / Leczenie
Eksperymentalny: Intervention group
Group A: Botulinum toxin A with placebo cream
Lek: Botulinum toxin A via microneedle
Botulinum toxin A plus cream placebo
Komparator placebo: Control group
Group B: Placebo botulinum A with isosorbide dinitrate cream
Inny: Control (Normal saline)
Normal saline via microneedles plus isosorbide dinitrate cream

Co mierzy badanie?

Podstawowe miary wyniku

Miara wyniku
Opis środka
Ramy czasowe
Change from baseline in distal digit temperature at 4 Weeks
Ramy czasowe: 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.
Baseline and 4 weeks after treatment

Miary wyników drugorzędnych

Miara wyniku
Opis środka
Ramy czasowe
Change from baseline in Raynaud's Phenomenon pain severity score on the Visual Analogue Scale (VAS)
Ramy czasowe: Baseline to 1 week, baseline to 4 weeks, and baseline to 12 weeks after treatment
The change in pain severity related to Raynaud's phenomenon is assessed using the Visual Analogue Scale (VAS). The VAS ranges from a minimum value of 0 to a maximum value of 100, where 0 represents no pain and 100 represents the worst imaginable pain. Higher scores indicate a worse outcome (greater pain intensity).
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
Ramy czasowe: 1 week, 4 weeks, and 12 weeks after treatment
The safety and tolerability of the intervention are evaluated by recording the number of participants who develop localized adverse events (including erythema, bleeding, dermatitis, local infection, or intolerable pain) at the microneedle pad application site.
1 week, 4 weeks, and 12 weeks after treatment
Change from baseline in Raynaud's Condition Score (RCS)
Ramy czasowe: Baseline to 1 week, baseline to 4 weeks, and baseline to 12 weeks after treatment
The daily clinical severity and frequency of Raynaud's phenomenon attacks are evaluated using the Raynaud's Condition Score (RCS). The RCS is a self-assessment scale ranging from 0 to 10, where 0 represents no difficulty or severity and 10 represents extreme difficulty or severity. Higher numerical values indicate greater symptom severity and functional impairment.
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)
Ramy czasowe: 1, 4, and 12 weeks
The progression of RP to DU using numbers of DU at 1, 4 , and 12 weeks after treatment
1, 4, and 12 weeks
The progression of Raynaud's phenomenon (RP) to digital ulcer (DU)
Ramy czasowe: 1, 4 , and 12 weeks after treatment
The progression of RP to DU using size in mm of DU at 1, 4 , and 12 weeks after treatment
1, 4 , and 12 weeks after treatment
The clinical benefit and safety of microneedle pad
Ramy czasowe: 1, 4, and 12 weeks
The clinical benefit and safety of microneedle pad by healthy assessment using Scleroderma Health Assessment Questionnaire (SHAQ) at 1, 4, and 12 weeks after treatment. The scores range from 0 to 3 for each symptom, with higher numerical values reflecting a higher degree of symptom intensity.
1, 4, and 12 weeks
The progression of Raynaud's phenomenon (RP) to digital ulcers (DUs)
Ramy czasowe: 1, 4 , and 12 weeks after treatment
The net ulcer burden of digital ulcers using Digital Ulcer Clinical Assessment Score (DUCAS) from 0-68 at 1, 4 , and 12 weeks after treatment. The higher Digital Ulcer Clinical Assessment Score values reflects a higher degree of symptom intensity
1, 4 , and 12 weeks after treatment
The clinical benefit and safety of microneedle pad
Ramy czasowe: 1, 4, and 12 weeks after treatment

The clinical benefit and quality of life are evaluated using the EuroQol 5-Dimension 3-Level (EQ-5D-3L) questionnaire, which consists of two parts. The first part comprises five specific dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 levels: 1 (no problems), 2 (some problems), and 3 (extreme problems). Selecting a level for each dimension generates a 5-digit health state profile (e.g., 11223). This profile ranges from a minimum value of 11111 to a maximum value of 33333, where higher numerical profiles indicate a worse outcome.

The second part features a standard 20-cm vertical Visual Analogue Scale where patients self-rate their overall health. The Visual Analogue Scale ranges from a minimum value of 0 ("the worst health you can imagine") to a maximum value of 100 ("the best health you can imagine"), where higher scores indicate a better outcome.
1, 4, and 12 weeks after treatment

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

Sponsor

Khon Kaen University

Współpracownicy

Srinagarind Hospital, Khon Kaen University
National Science and Technology Development Agency, Thailand

Daty zapisu na studia

Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.

Główne daty studiów

Rozpoczęcie studiów (Szacowany)

1 sierpnia 2026

Zakończenie podstawowe (Szacowany)

31 lipca 2028

Ukończenie studiów (Szacowany)

31 grudnia 2028

Daty rejestracji na studia

Pierwszy przesłany

3 maja 2026

Pierwszy przesłany, który spełnia kryteria kontroli jakości

6 sierpnia 2026

Pierwszy wysłany (Rzeczywisty)

12 sierpnia 2026

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Rzeczywisty)

17 sierpnia 2026

Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości

13 sierpnia 2026

Ostatnia weryfikacja

1 sierpnia 2026

Więcej informacji

Terminy związane z tym badaniem

Słowa kluczowe

Dodatkowe istotne warunki MeSH

Inne numery identyfikacyjne badania

  • Botox for scleroderma-Raynaud
  • Khon Kaen University (Inny identyfikator: Khon Kaen University)

Plan dla danych uczestnika indywidualnego (IPD)

Planujesz udostępniać dane poszczególnych uczestników (IPD)?

NIEZDECYDOWANY

Informacje o lekach i urządzeniach, dokumenty badawcze

Bada produkt leczniczy regulowany przez amerykańską FDA

Nie

Bada produkt urządzenia regulowany przez amerykańską FDA

Nie

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