The Therapeutic Effect of Thalidomide in Syringomyelia

Официальное название

The Effect of Thalidomide in Refractory Syringomyelia（RS）: a Phase II Clinical Trial

Обзор

Purpose: This phase II clinical trial aims to evaluate the indications, therapeutic effects and side effects of thalidomide in refractory syringomyelia. Primary outcome measure: The primary endpoint is the change of ASIA at week 12. The clinical efficacy is defined as ASIA increase ≥ 1 at week 12, as compared with that before thalidomide usage.

Подробное описание

The pathogenesis of syringomyelia is poorly understood and duraplasty or shunting is not always effective. Although it is generally thought that syringomyelia is simply an accumulation of CSF from the subarachnoid space, the pathogenesis is likely to be more complex and may involve cellular and molecular processes.

The investigators supposed that blood spinal cord barrier(BSCB) might play a key role in the pathogenesis of syringomyelia, especially post-traumatic syringomyelia(PTS), and that thalidomide, as an BSCB protection-related drug, would reduce BSCB damage and protect BSCB in syringomyelia.

Primary objectives: This phase II clinical trial aims to evaluate the indications, therapeutic effects and safety of thalidomide in refractory syringomyelia.

Вмешательства

• Препарат Thalidomide
  Thalidomide 50 - 200 mg once at nightime

Первичные конечные точки

• ASIA Score [Срок оценки: 1 day before and 3 days, 3 months after drug treatment]

Вторичные конечные точки (7)

• syringomyelia remission [Срок оценки: 1 day before and 3 days, 3 months after drug treatment]
• The evoked electromyographic signal (eEMG) potential [Срок оценки: 1 day before and 3 days, 3 months after drug treatment]
• Visual Analog Scale (VAS) [Срок оценки: 1 day before and 3 days, 3 months after drug treatment]
• Klekamp and Sammi syringomyelia scale [Срок оценки: 1 day before and 3 days, 3 months after drug treatment]
• modified Japanese Orthopaedic Association Scores (mJOA) [Срок оценки: 1 day before and 3 days, 3 months after drug treatment]
• xuanwu syringomyelia scale [Срок оценки: 1 day before and 3 days, 3 months after drug treatment]
• Incidence of complications [Срок оценки: 1 day before and 3 days, 3 months after drug treatment]

Критерии участия

Критерии включения

• Contraindication to duraplasty and shunting treatment due to history or high risk of severe adverse effects,
• or non-effective response to duraplasty and shunting treatment in 12 months prior to study entry.
• Estimated life expectancy must be greater than 12 months.
• Routine laboratory studies: bilirubin </=1.0 \* upper limits of normal (ULN); aspartate aminotransferase (AST or SGOT) or alanine aminotransferase (ALT)< 1.0 \* ULN; creatinine <1.0 \* ULN; white-cell count >/= 4,000 per cubic millimeter; neutrophils count >/=1500 per cubic millimeter platelets >/= 100,000 per cubic millimeter; Hb >/=110 gram per millilitres; PT, APTT, INR in a normal range.
• Ability to understand and willingness to sign a written informed consent document, or constant caregivers who well understand and willingness to sign a written informed consent document.
• Must be able to swallow tablets

Критерии исключения

• Evidence of tumor metastasis, recurrence, or invasion;
• History of psychiatric diseases ;
• History of seizures;
• History of arteriosclerotic cardiovascular diseases (ASCVD), e.g. stroke, myocardial infaction, unstable angina, within 6 months;
• New York Heart Association Grade II or greater congestive heart failure;
• Serious and inadequately controlled cardiac arrhythmia;
• Significant vascular disease, e.g. moderate or severe carotid stenosis, aortic aneurysm, history of aortic dissection;
• Severe infection;
• History of allergy to relevant drugs;
• Pregnancy, lactation, or fertility program in the following 12 months;
• History or current diagnosis of peripheral nerve disease;
• Abnormal in liver and renal function;
• Active tuberculosis;
• Transplanted organs;
• Human immunodeficiency virus;
• Participation in other experimental studies.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Fengzeng Jian — Пекин

Публикации

• Chen H, Wu S, Tang M, Zhao R, Zhang Q, Dai Z, Gao Y, Yang S, Li Z, Du Y, Yang A, Zhong L, Lu L, Xu L, Shen X, Liu S, Zhong J, Li X, Lu H, Xiong H, Shen Y, Chen H, Gong S, Xue H, Ge Z. Thalidomide for Recurrent Bleeding Due to Small-Intestinal Angiodysplasia. N Engl J Med. 2023 Nov 2;389(18):1649-1659. doi: 10.1056/NEJMoa2303706. PMID 37913505
• Guan J, Yuan C, Yao Q, Du Y, Fang Z, Zhang L, Jia S, Zhang C, Liu Z, Wang K, Duan W, Wang Z, Wang X, Wu H, Chen Z, Jian F. A novel scoring system for assessing adult syringomyelia associated with CM I treatment outcomes. Acta Neurol Belg. 2023 Jun;123(3):807-814. doi: 10.1007/s13760-023-02264-4. Epub 2023 Apr 12. PMID 37046133
• Hemley SJ, Bilston LE, Cheng S, Stoodley MA. Aquaporin-4 expression and blood-spinal cord barrier permeability in canalicular syringomyelia. J Neurosurg Spine. 2012 Dec;17(6):602-12. doi: 10.3171/2012.9.SPINE1265. Epub 2012 Oct 19. PMID 23082850
• Yuan C, Xia P, Duan W, Wang J, Guan J, Du Y, Zhang C, Liu Z, Wang K, Wang Z, Wang X, Wu H, Chen Z, Jian F. Long-Term Impairment of the Blood-Spinal Cord Barrier in Patients With Post-Traumatic Syringomyelia and its Effect on Prognosis. Spine (Phila Pa 1976). 2024 Mar 15;49(6):E62-E71. doi: 10.1097/BRS.0000000000004884. Epub 2023 Nov 28. PMID 38014747
• Heiss JD. Cerebrospinal Fluid Hydrodynamics in Chiari I Malformation and Syringomyelia: Modeling Pathophysiology. Neurosurg Clin N Am. 2023 Jan;34(1):81-90. doi: 10.1016/j.nec.2022.08.007. Epub 2022 Nov 3. PMID 36424067
• Guan J, Yuan C, Zhang C, Ma L, Yao Q, Cheng L, Liu Z, Wang K, Duan W, Wang X, Wu H, Chen Z, Jian F. Intradural Pathology Causing Cerebrospinal Fluid Obstruction in Syringomyelia and Effectiveness of Foramen Magnum and Foramen of Magendie Dredging Treatment. World Neurosurg. 2020 Dec;144:e178-e188. doi: 10.1016/j.wneu.2020.08.068. Epub 2020 Aug 15. PMID 32805463
• Liu S, Ma L, Qi B, Li Q, Chen Z, Jian F. Suppression of TGFbetaR-Smad3 pathway alleviates the syrinx induced by syringomyelia. Cell Biosci. 2023 May 29;13(1):98. doi: 10.1186/s13578-023-01048-w. PMID 37248485

Идентификаторы

NCT: NCT06268093 · XWTETS

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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