The Therapeutic Effect of Thalidomide in Syringomyelia

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

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.

Study Overview

• Status: Recruiting
• Conditions: Syringomyelia; Thalidomide
• Intervention / Treatment: Drug: Thalidomide

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: fengzeng jian; Phone Number: +861083198899; Email: jianfengzeng@xwh.ccmu.edu.cn
• Study Contact Backup: Name: chenghua yuan; Phone Number: +861083198899; Email: yuanchenghua@ccmu.edu.cn

Study Locations

• China
  • Beijing City
    • Beijing, Beijing City, China, 100032
      • Recruiting
      • Fengzeng Jian
      • Contact: fengzeng jian, md; Email: jianfengzeng@xwh.ccmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Thalidomide; Oral Thalidomide	Drug: Thalidomide; Thalidomide 50 - 200 mg once at nightime

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
Incidence of complications	Incidence of complications	1 day before and 3 days, 3 months after drug treatment

Collaborators and Investigators

• Sponsor: Xuanwu Hospital, Beijing
• Investigators: Study Chair: fengzeng jian, Xuanwu Hospital, Beijing

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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). 2023 Nov 28. doi: 10.1097/BRS.0000000000004884. Online ahead of print.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2024
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2028

Study Registration Dates

• First Submitted: February 7, 2024
• First Submitted That Met QC Criteria: February 19, 2024
• First Posted (Actual): February 20, 2024

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 19, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Syringomyelia; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Thalidomide
• Other Study ID Numbers: XWTETS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No