Clinical trial NCT03262844: Efficacy and Safety of Nerve Root Axial Decompression Surgery in The Treatment of Tethered Cord Syndrome
Official title: Efficacy and Safety of Nerve Root Axial Decompression Surgery in The Treatment of Tethered Cord Syndrome: A Conservative Treatment- Controlled, Randomized, Clinical Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Tethered Cord Syndrome
Lead sponsor: Shanghai Changzheng Hospital
Sponsor class: OTHER
First posted: 2017-08-25
Enrollment: 36
Sex: ALL
Minimum age (years): 14
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Background: Tethered cord syndrome (TCS) is a progressive clinical condition including a series of neurological dysfunctions and deformities attributable to abnormally increased tension on the spinal cord, which is lacking effective treatment to relieve the symptoms and prevent progression. Dr. Shi recently proposed a new technique as nerve root axial decompression surgery, which is also called capsule surgery, to treat patients with TCS. Yet, the effectiveness and safety should be further studied.

Purpose: The aim of this study is to compare the effectiveness and safety of clinical outcomes between capsule surgery and conservative treatment in patients with TCS. A study hypothesis is that outcomes will be improved after capsule surgery.

Methods: This study is a randomized clinical trial with a two-factor (2x7) research design. The TCS patients will be randomly assigned in one of the two treatment groups: capsule surgery and conservative treatment. Seven outcome measures will be collected pre-operative for baseline, and then at1, 12, 24, 48, and 96 weeks post-operative follow-up visits, including: International Consultation on Incontinence Modular Questionnaire Short Version (ICI-Q-SF), Rintala Score, a new developed Chinese version of questionnaire, Oswestry disability index (ODI), SF-12, foot function index (FFI) and Pirani score. Urodynamic testing, bladder ultrasonography, electromyogram, muscle strength and sensation of lower limbs will be obtained before and post treatment, to determine the patient's function of lower limbs. The investigator performing the outcome measures will be blinded to group assignment, and therefore will not participate in treatment. After randomization, the conservative group will be followed up in the outpatient clinic. The capsule surgery group will receive the nerve root axial decompression surgery (capsule surgery).

Data Analysis: Two 2x7 MANOVAs with repeated measures will be used to examine the differences in the seven measures between groups and at the five different time frames with the α level set at 0.05. Non-parametric tests (Mann-Whitney U tests) will be used to compare the differences in the urodynamics and muscle strength data over time and between groups.

Detailed description: Background: Tethered cord syndrome (TCS) is a progressive clinical condition including a series of neurological dysfunctions and deformities attributable to abnormally increased tension on the spinal cord. The standard surgical treatment is untethering the spinal cord and correction of the related deformity. Although reported results are encouraging, it continues to pose challenges on management of TCS patients. Symptomatic re-tethering seems to be an inevitable result, which occurs in 20%-50% patients after untethering. Recently, filum dissection was found no good to improve urinary symptoms compared to conservative treatment in teenagers as reported in an RCT study. Also, it remained controversy when to perform the surgery and how to evaluate the benefits of surgery or conservative treatment. Dr. Shi recently proposed a new technique as nerve root axial decompression surgery, which is also called capsule surgery, to treat patients with TCS. Yet, the effectiveness and safety should be further studied.

Purpose: The aim of this study is to compare the effectiveness and safety of clinical outcomes between capsule surgery and conservative treatment in patients with TCS. A study hypothesis is that outcomes will be improved after capsule surgery.

Methods: This study is a randomized clinical trial with a two-factor (2x7) research design. The TCS patients will be randomly assigned in one of the two treatment groups: capsule surgery and conservative treatment. Seven outcome measures will be collected pre-operative for baseline, and then at1, 12, 24, 48, and 96 weeks post-operative follow-up visits, including: (1) International Consultation on Incontinence Modular Questionnaire Short Version (ICI-Q-SF) to assess the urinary functions, (2) Rintala Score for bowel function, (3) a new developed Chinese version of questionnaire to assess the quality of life in patients and parents due to bladder dysfunction. (4) Oswestry disability index (ODI) to assess the function of back and lower limbs, (5)SF-12 for whole quality of life, (6) Pirani score to assess clubfoot deformity, and (7) foot function index to assess the impacts on quality of life due to clubfoot. Urodynamics, bladder ultrasonography, muscle strength and sensation of lower limbs will be obtained before and post treatment, to determine the patient's function of lower limbs. The investigator performing the outcome measures will be blinded to group assignment, and therefore will not participate in treatment. After randomization, the conservative group will be followed up in the outpatient clinic. The capsule surgery group will receive the nerve root axial decompression surgery.

Data Analysis: Two 2x7 MANOVAs with repeated measures will be used to examine the differences in the four measures between groups and at the five different time frames with the α level set at 0.05. Non-parametric tests (Mann-Whitney U tests) will be used to compare the differences in the urodynamics and muscle strength data over time and between groups.

Eligibility criteria: Inclusion Criteria:

1. patients aged 14-20 years, without gender limitation, are willing to sign informed consent;
2. patients diagnosed with tethered cord syndrome (TCS);
3. patients accepted untethering surgery or resection of intra-lipomas or myelomeningocele after birth;
4. patients present with the recent occurrence of bladder or bowel dysfunction, with progressive deterioration, may be accompanied by motor deficits of lower extremity;
5. urodynamic examination suggests neurogenic injury;
6. the current conventional treatment is difficult to achieve satisfactory clinical outcomes.

Exclusion Criteria:

1. bladder or ureter obstruction;
2. other types of neurogenic bladder dysfunction (spinal cord injury, cerebral palsy, other brain injuries);
3. anorectal malformations;
4. poor health condition, unable to tolerate surgery;
5. patients (or their guardians) cannot give full informed consent for cognitive dysfunction;
6. patients who have participated in other clinical trials in the past 1 month.
7. patients with active hepatitis B (including HBeAg) or serological markers (HBsAg or / and HBeAg or / and HBcAb), hepatitis C, tuberculosis, cytomegalovirus infection, severe fungal infection or HIV infection;
8. patients with active peptic ulcers within 3 months before randomization.
9. patients with malignant neoplasms

Primary outcomes:
measure: Changes of patient-reported scores assessing bladder function
timeFrame: At 1 week pre- and 1, 12, 24, 48, and 96 weeks post-operative follow-up visits.
Secondary outcomes:
measure: Changes of patient-reported scores assessing bowel function
timeFrame: At 1 week pre- and 1, 12, 24, 48, and 96 weeks post-operative follow-up visits.
measure: Changes of patient-reported quality of life due to bladder dysfuction
timeFrame: At 1 week pre- and 1, 12, 24, 48, and 96 weeks post-operative follow-up visits.
measure: Bladder function
timeFrame: At 1 week pre- and 1, 12, 48, and 96 weeks post-operative follow-up visits.
measure: Muscle power
timeFrame: At 1 week pre- and 1, 12, 24, 48, and 96 weeks post-operative follow-up visits.
measure: Improvment of clubfoot deformity
timeFrame: At 1 week pre- and 1, 12, 24, 48, and 96 weeks post-operative follow-up visits.
measure: Changes of patient-reported scores assessing foot deformity
timeFrame: At 1 week pre- and 1, 12, 24, 48, and 96 weeks post-operative follow-up visits.
measure: Changes of patient-reported scores assessing function of back and lower limbs
timeFrame: At 1 week pre- and 1, 12, 24, 48, and 96 weeks post-operative follow-up visits.
measure: Changes of patient-reported quality of life
timeFrame: At 1 week pre- and 1, 12, 24, 48, and 96 weeks post-operative follow-up visits.
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Changzheng Hospital
state: Shanghai
Study officials:
affiliation: Shanghai Changzheng Hospital, Second Military Medical University
name: Jiangang Shi, MD
role: STUDY_CHAIR
References:
citation: Steinbok P, MacNeily AE, Hengel AR, Afshar K, Landgraf JM, Hader W, Pugh J. Filum Section for Urinary Incontinence in Children with Occult Tethered Cord Syndrome: A Randomized, Controlled Pilot Study. J Urol. 2016 Apr;195(4 Pt 2):1183-8. doi: 10.1016/j.juro.2015.09.082. Epub 2016 Feb 28.