Ultrasound-assisted vs Landmark Based Intrathecal Administration of Nusinersen
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| ClinicalTrials.gov Identifier: NCT04674618 |
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Recruitment Status :
Recruiting
First Posted : December 19, 2020
Last Update Posted : January 20, 2022
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Intrathecal administration of Nusinersen, an antisense oligonucleotide capable of increasing Survival Motor Neuron protein production, has been tested in Spinal Muscular Atrophy (SMA) to improve motor function and survival. A feature of adult SMA patients is a progressive neuromyopathic scoliosis, so spinal nusinersen administration can be challenging. Landmark identification using a pre-procedure ultrasound (US) facilitates technical performance of spinal anesthesia and allows for the elimination of radiation exposure.
The aim of this randomized prospectic study is to determine if the US assistance for spinal administration of nusinersen is able to increase the proportion at successful 1st needle insertion of the needle. Secondary outcome measures are procedure time, patient satisfaction and prevalence of postdural puncture headache.
Patients will be randomlized to receive a US-assisted nusinersen administration or a landmark based nusinersen administration.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Muscular Atrophy, Spinal Ultrasound | Device: US-assisted nusinersen administration | Not Applicable |
Background Nusinersen, an antisense oligonucleotide (ASO) capable of increasing SMN protein production, has been used in clinical trials in infants and children with SMA type 1 or type 2 and has been associated to a significantly better motor development, motor function, and survival compared with placebo groups. Because of the lacking ability of ASOs to cross the blood-brain barrier, nusinersen is administered intrathecally. While most infants with SMA type 1 die in easy childhood without a muscular and nutritional support, SMA type 2 patients often reach adulthood, and patients with SMA type 3 generally have a normal lifespan. A further feature of SMA patients is a progressive neuromyopathic scoliosis, so spinal nusinersen administration can be challenging because of poorly palpable surface landmarks, as in elderly and in obese patients. In patients with anticipated difficult anatomy, the failure rate of neuraxial anesthesia may be as high as 17%. Furthermore, multiple needle punctures are associated with hematoma, post-dural-puncture headache, back pain, and patient dissatisfaction. Current data suggest that landmark identification using a pre-procedure ultrasound (US) is a useful adjunct to neuraxial anesthesia that facilitates technical performance in obstetric and pediatric patients. In adult patients with difficult spinal anatomy a pre-procedure US reduces the number of attempts and the number of needle passes necessary for successful spinal anesthesia and can predict technical difficulty; notably, compared to fluoroscopy, sonography allows for the elimination of radiation exposure for patient and physician and for a cost reduction for institution. Despite these potential advantages, reports of lumbar central neuraxial blocks US guidance in patients with predicted placement difficulties are limited. Most reports to date involve a small number of patients with normal anatomy.
Methods The study will be conducted in Fondazione Policlinico "A.Gemelli" operatory rooms, Rome, Italy. Written informed consent will be obtained from all patients enrolled in the study. SMA adult patients referring to NEMO center of this institution will be enrolled. Exclusion criteria will be: coagulation defects, patients medicated with anticoagulation, any finding of infection in puncture site, high intracranial pressure. A visit will be performed before the procedure.
Patients will be randomly assigned in ratio 1:1 to one of two groups using a sealed envelope: Group 1 (US-assisted nusinersen administration) and Group 2 (landmark based nusinersen administration). Nusinersen administration will be performed with a single-operator technique by one of two anesthesiologists trained on US-guided or -assisted central neuraxial blocks. With patient in sitting position, or in lateral position if forced posture will be needed, after skin disinfection with 2% chlorhexidine in 70% alcohol, the spinal administration will be performed as follows: Group 1 (US- guided nusinersen administration). The paramedian sagittal oblique view will be used to identify specific lumbar interspaces and perform the procedure. Starting at the sacrum and moving cephalad, the L2-3 or L3-4 intervertebral interspace will be identified. After local anesthesia with lidocaine 2% (3-5 mL), a 25-gauge Withacre spinal needle will be used to identify subarachnoid space. After confirmation of the flow of cerebrospinal fluid and after removing 5 ml of CSF, nusinersen will be administered intrathecally over 1-3 min. Group 2 (landmark based nusinersen administration).
The desired intervertebral space (L2-3 or L3-4) was first identified by manual palpation of surface landmarks and marked on the skin. After local anesthesia with lidocaine 2% (3-5 mL) a 25-gauge Withacre spinal needle will be used. After confirmation of the flow of cerebrospinal fluid and after removing 5 ml of CSF, nusinersen will be administered as previously described. After successful administration, patients will be positioned in the supine position for 2-3 h. Within 72 hours of administration a phone survey will be conducted to evaluate the development of postdural puncture headache. Another outpatient visit will be performed at 30 days after the procedure.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 58 participants |
| Allocation: | Randomized |
| Intervention Model: | Crossover Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Ultrasound-assisted vs Landmark Based Intrathecal Administration of Nusinersen in Adult Patients With SMA Disease: a Randomized Trial |
| Actual Study Start Date : | December 14, 2020 |
| Actual Primary Completion Date : | December 14, 2021 |
| Estimated Study Completion Date : | December 14, 2022 |
| Arm | Intervention/treatment |
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Experimental: US-assisted nusinersen administration
A paramedian sagittal oblique view will be used to identify with ultrasound specific lumbar interspaces. After local anesthesia the spinal needle will be used to identify subarachnoid space. After confirmation of the flow of cerebrospinal fluid and after removing 5 ml of CSF, nusinersen will be administered intrathecally over 1-3 min.
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Device: US-assisted nusinersen administration
Ultrasound identification of intervertebral space (L2-L3 or L3-L4) |
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No Intervention: landmark based nusinersen administration
The desired intervertebral space will be first identified by manual palpation of surface landmarks and marked on the skin. After local anesthesia the spinal needle will be usedto identify subarachnoid space. After confirmation of the flow of cerebrospinal fluid and after removing 5 ml of CSF, nusinersen will be administered intrathecally over 1-3 min.
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- Number of attempts [ Time Frame: During the procedure (spinal injection of nusinersen) ]The number of needle insertions through the skin surface. If complete withdrawal of the needle from the patient's skin surface will be needed, followed by reinsertion in a different skin location or a different spinal level, this will be counted as a second attempt.
- Successful administration [ Time Frame: During the procedure (spinal injection of nusinersen) ]confirmation of the flow of cerebrospinal fluid through the spinal needle and subsequent nusinersen administration
- Procedure time [ Time Frame: During the procedure (spinal injection of nusinersen) ]the time in seconds from the start of US imaging to visualization of cerebrospinal fluid flow in intervention group and from the first hand contact to the skin to visualization of cerebrospinal fluid flow in control group.
- Patients satisfaction [ Time Frame: 5 minutes after the end of the procedure (spinal injection of nusinersen) ]will be evaluated with a five-point Likert Scale (from a value of 1- extremely unsatisfied to a value of 5-extremely satisfied)
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- SMA adult patients
Exclusion Criteria:
- coagulation defects;
- medication with anticoagulant;
- infection in puncture site;
- high intracranial pressure
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04674618
| Italy | |
| IRCCS Policlinico Agostino Gemelli | Recruiting |
| Rome, Italy, 00168 | |
| Contact: Luciano Frassanito, MD +393475256158 luciano.frassanito@policlinicogemelli.it | |
| Responsible Party: | Fondazione Policlinico Universitario Agostino Gemelli IRCCS |
| ClinicalTrials.gov Identifier: | NCT04674618 |
| Other Study ID Numbers: |
3352 |
| First Posted: | December 19, 2020 Key Record Dates |
| Last Update Posted: | January 20, 2022 |
| Last Verified: | February 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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Muscular Atrophy Muscular Atrophy, Spinal Atrophy Pathological Conditions, Anatomical Neuromuscular Manifestations Neurologic Manifestations |
Nervous System Diseases Spinal Cord Diseases Central Nervous System Diseases Motor Neuron Disease Neurodegenerative Diseases Neuromuscular Diseases |