Ultrasound-assisted vs Landmark Based Intrathecal Administration of Nusinersen

February 20, 2024 updated by: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Ultrasound-assisted vs Landmark Based Intrathecal Administration of Nusinersen in Adult Patients With SMA Disease: a Randomized Trial

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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

Enrollment (Actual)

58

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Rome, Italy, 00168
        • IRCCS Policlinico Agostino Gemelli

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • SMA adult patients

Exclusion Criteria:

  • coagulation defects;
  • medication with anticoagulant;
  • infection in puncture site;
  • high intracranial pressure

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Device: US-assisted nusinersen administration
Ultrasound identification of intervertebral space (L2-L3 or L3-L4)
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
During the procedure (spinal injection of nusinersen)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
During the procedure (spinal injection of nusinersen)
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.
During the procedure (spinal injection of nusinersen)
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)
5 minutes after the end of the procedure (spinal injection of nusinersen)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 14, 2020

Primary Completion (Actual)

December 14, 2021

Study Completion (Actual)

December 21, 2023

Study Registration Dates

First Submitted

December 10, 2020

First Submitted That Met QC Criteria

December 17, 2020

First Posted (Actual)

December 19, 2020

Study Record Updates

Last Update Posted (Estimated)

February 21, 2024

Last Update Submitted That Met QC Criteria

February 20, 2024

Last Verified

July 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3352

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Muscular Atrophy, Spinal

Clinical Trials on US-assisted nusinersen administration

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Madagascar

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe