The Therapeutic Effect of Thalidomide in Syringomyelia

Syringomyelia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06268093
• Other study ID #: XWTETS
• Status: Recruiting
• Phase: Phase 2
• Start date: February 2024
• Est. completion date: February 2028

Study information

• Verified date: February 2024
• Source: Xuanwu Hospital, Beijing
• Contact: fengzeng jian
• Phone: +861083198899
• Email: jianfengzeng[@]xwh.ccmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: February 2028
• Est. primary completion date: February 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Syringomyelia
• Thalidomide

Intervention

Drug:
• Thalidomide
Thalidomide 50 - 200 mg once at nightime

Locations

Country	Name	City	State
China	Fengzeng Jian	Beijing	Beijing City

Sponsors (1)

Lead Sponsor	Collaborator
Xuanwu Hospital, Beijing

Country where clinical trial is conducted

China, 

References & Publications (7)

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. — View Citation

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. — View Citation

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 Treatmen — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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 Posttraumatic Syringomyelia and its Effect on Prognosis. Spine (Phila Pa 1976 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ASIA Score	American Spinal Injury Association(ASIA) Score for evaluating the spinal cord function, degree of the spinal cord function, motor1-100, sensory 1-224, higher scores mean a better outcome	1 day before and 3 days, 3 months after drug treatment
Secondary	syringomyelia remission	syringomyelia remission is defined as = 25% reduction in syringomyelia volume on T2 images at week 12, as compared with that before thalidomide usage	1 day before and 3 days, 3 months after drug treatment
Secondary	The evoked electromyographic signal (eEMG) potential	The evoked electromyographic signal (eEMG) potential is the standard index	1 day before and 3 days, 3 months after drug treatment
Secondary	Visual Analog Scale (VAS)	degree of the pain, 1-10, higher scores mean a worse outcome	1 day before and 3 days, 3 months after drug treatment
Secondary	Klekamp and Sammi syringomyelia scale	for evaluating the spinal cord function, higher scores mean a better outcome	1 day before and 3 days, 3 months after drug treatment
Secondary	modified Japanese Orthopaedic Association Scores (mJOA)	Motor function, sensory, bladder function;for evaluating the spinal cord function;0-17, higher scores mean a better outcome	1 day before and 3 days, 3 months after drug treatment
Secondary	xuanwu syringomyelia scale	for evaluating the spinal cord function, for evaluating the spinal cord function;0-18, higher scores mean a worse outcome	1 day before and 3 days, 3 months after drug treatment
Secondary	Incidence of complications	Incidence of complications	1 day before and 3 days, 3 months after drug treatment