Radiosurgery for Spasticity

(SPASM Trial)

Recruiting at 3 trial locations

Overseen By Uchechi Okafor, BS

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: Ohio State University

Disqualifiers: Pregnancy, Inability to lie supine, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 day

22 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to help individuals with spasticity, characterized by very tight muscles. The treatment, called stereotactic radiosurgery dorsal rhizotomy, uses precise radiation beams aimed at nerves in the back to relax the muscles. Participants will be randomly assigned to either a real treatment group or a "sham" group (a control group that does not receive the actual treatment) to determine the real treatment's effectiveness. Individuals with long-term spasticity unresponsive to medication might be suitable for this trial. After six months, those in the sham group can opt to receive the real treatment. As an unphased trial, this study provides a unique opportunity for patients to explore innovative treatment options that might not be available elsewhere.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, since the trial is for people whose spasticity is not helped by their current medications, you might be able to continue them. It's best to ask the trial organizers for more details.

What prior data suggests that stereotactic radiosurgery dorsal rhizotomy is safe for treating spasticity?

Research shows that stereotactic radiosurgery dorsal rhizotomy uses precise radiation beams to target specific nerves in the back, aiming to reduce muscle stiffness, or spasticity. Studies on similar treatments have shown they can effectively reduce spasticity.

While direct safety data for this exact procedure is unavailable, similar treatments like selective dorsal rhizotomy have managed spasticity in children and young adults. These treatments are generally well-tolerated, though they can have side effects, as with any medical procedure.

The current trial does not focus on testing the treatment's safety in a new phase, indicating that the safety of this type of treatment is already somewhat understood. However, participants should discuss any concerns with their healthcare provider to understand potential risks. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the potential of stereotactic radiosurgery dorsal rhizotomy for treating spasticity because it offers a non-invasive approach, unlike traditional surgical options like selective dorsal rhizotomy. This treatment uses precise radiation to target the nerves responsible for muscle overactivity, potentially reducing spasticity without the need for incisions or long recovery times. By focusing radiation on specific neural pathways, it aims to provide relief with minimal side effects, which could be a game-changer for patients seeking alternatives to surgery or invasive procedures.

What evidence suggests that stereotactic radiosurgery dorsal rhizotomy is effective for spasticity?

In this trial, participants will receive either stereotactic radiosurgery dorsal rhizotomy (SRS) or a sham treatment. Research shows that SRS uses precise radiation to target specific nerves, helping to reduce muscle tightness. This treatment builds on the well-known procedure called selective dorsal rhizotomy (SDR), which reduces muscle stiffness in conditions like cerebral palsy. Studies have shown that SDR effectively lowers muscle stiffness and improves movement in children and young adults. The radiosurgery version aims to achieve similar results with a less invasive approach. Overall, early findings suggest it could be a promising option for easing muscle stiffness. ^{1 2 4 5 6}

Who Is on the Research Team?

Joshua Palmer, MD

Principal Investigator

Ohio State University

Are You a Good Fit for This Trial?

This trial is for individuals over 16 years old with chronic spasticity from conditions like stroke, SCI, or cerebral palsy that doesn't improve with medication. If under 18, parental consent is needed. It's not for those who can't lie on their back for the procedure, if the target nerve isn't visible on scans, or if pregnant.

Inclusion Criteria

I am older than 16 and if under 18, my parents have agreed to sign the consent.

My severe muscle stiffness hasn't improved with medication.

Exclusion Criteria

I cannot lie on my back for treatments.

The nerve we need to see cannot be seen on a CT or MRI scan.

I am not pregnant or have confirmed I am not pregnant through a test.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either stereotactic radiosurgery dorsal rhizotomy or a sham treatment

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in spasticity and quality of life

6 months

Multiple visits (in-person and virtual)

Crossover Treatment

Participants who received the sham treatment are eligible to receive the real treatment

1 day

1 visit (in-person)

Long-term Follow-up

Participants are monitored for long-term changes in spasticity-related quality of life

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Sham
• Stereotactic Radiosurgery Dorsal Rhizotomy

Trial Overview The study tests a treatment called stereotactic radiosurgery dorsal rhizotomy which aims to reduce muscle stiffness by targeting nerves with radiation. Participants are randomly assigned to receive either this real treatment or a sham (fake) procedure to compare outcomes.

How Is the Trial Designed?

Group I: SRS Treatment Active Control 1 Intervention

Group II: Sham Treatment Placebo Group 1 Intervention

No intervention but can crossover after 6 months

Stereotactic Radiosurgery Dorsal Rhizotomy is already approved in United States, European Union for the following indications:

Approved in United States as Stereotactic Radiosurgery Dorsal Rhizotomy for:

• Spasticity associated with stroke
• Spasticity associated with spinal cord injury
• Spasticity associated with cerebral palsy

Approved in European Union as Selective Dorsal Rhizotomy for:

• Spasticity in children with cerebral palsy
• Spasticity in adults with spinal cord injury

Who Is Running the Clinical Trial?

Ohio State University

Lead Sponsor

Trials

891

Recruited

2,659,000+

Centro Diagnostico Milano, Co-PI: Pantaleo Romanelli, MD

Collaborator

Trials

1

Recruited

20+

Varian Medical Systems

Industry Sponsor

Trials

63

Recruited

3,700+

Dow R. Wilson

Varian Medical Systems

Chief Executive Officer since 2012

MBA from Dartmouth's Amos Tuck School of Business, BA from Brigham Young University

Dr. Deepak Khuntia

Varian Medical Systems

Chief Medical Officer since 2020

MD from the University of Cambridge, PhD from the University of Leicester

Published Research Related to This Trial

Selective dorsal rhizotomy significantly alleviates spasticity in children with cerebral palsy, as evidenced by improved knee and hip ranges of motion that approached normal limits after 10 years.

The study, which involved 11 children with spastic diplegia and used quantitative gait analysis over a long-term follow-up, demonstrated lasting functional benefits in gait, although step length and velocity remained below normal levels after a decade.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gait before and 10 years after rhizotomy in children with cerebral palsy spasticity. Subramanian, N., Vaughan, CL., Peter, JC., et al.[2022]

Two cases of spinal cord tethering were reported as a previously unrecognized complication following selective dorsal rhizotomy (SDR) performed below the conus medullaris in children with spastic diparetic cerebral palsy.

Both patients initially showed improvement in spasticity and gait after SDR, but later developed urinary incontinence, highlighting the need for careful monitoring for this rare complication post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spinal cord tethering after selective dorsal rhizotomy below the conus medullaris. Belanger, K., McKay, W., Oleszek, J., et al.[2022]

In a study of 140 children with cerebral palsy undergoing selective dorsal rhizotomy (SDR), obesity was identified as a significant predictor of complications, including prolonged wound healing and superficial surgical site infections, with a notable odds ratio of 24.4 for wound healing issues.

The study found that while SDR is generally safe across all Gross Motor Functional Classification System (GMFCS) levels, non-ambulatory children (GMFCS IV and V) were more likely to require extended epidural pain management, highlighting the need for careful monitoring in this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of postoperative complications after selective dorsal rhizotomy. Wach, J., Yildiz, ÖC., Sarikaya-Seiwert, S., et al.[2021]

In a study of 38 patients with cerebral palsy undergoing single-level selective dorsal rhizotomy (SDR), it was found that ventral roots activated more muscles at lower stimulus thresholds compared to dorsal roots, indicating a clear physiological distinction that can guide surgical procedures.

The study established that approximately 64.72% of each rootlet was transected during SDR, and emphasized the need for individualized treatment plans due to variability in physiological responses among patients, including some with abnormal response characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electrophysiology of Sensory and Motor Nerve Root Fibers in Selective Dorsal Rhizotomies. Martinez, V., Browd, S., Osorio, M., et al.[2020]

Selective dorsal rhizotomy (SDR) has been successfully used to treat trauma-induced spasticity, showing favorable outcomes in both children and adults with cerebral palsy, as well as in post-traumatic cases.

The procedure has demonstrated minimal complications, suggesting that SDR could be a valuable treatment option for patients suffering from disabling spasticity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of selective dorsal rhizotomy in the management of post-traumatic spasticity: systematic review. Agrawal, M., Samala, R., Doddamani, R., et al.[2021]

A survey of 19 centers performing lumbosacral selective dorsal rhizotomy (SDR) for spastic cerebral palsy revealed significant variation in electrophysiologic techniques, with only 11 out of 15 centers consistently using unipolar stimulating electrodes.

Despite some consistent practices, such as recording from multiple lower limb muscles and using tetanic stimulation, there was notable disagreement on key aspects like the type of stimulator used and how to define response thresholds, indicating a lack of standardization in the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Variation between centers in electrophysiologic techniques used in lumbosacral selective dorsal rhizotomy for spastic cerebral palsy. Steinbok, P., Kestle, JR.[2018]

Selective dorsal rhizotomy (SDR) was found to be safe for adult patients with chronic spinal cord injury-induced spasticity, with no adverse events reported during the study involving 10 participants.

All secondary outcome measures, including spasticity and independence scores, showed significant improvement after SDR, suggesting potential efficacy in reducing spasticity and enhancing mobility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Potential Efficacy of Selective Dorsal Rhizotomy in Adults with Spinal Cord Injury-Induced Spasticity: An Open-Label, Non-Randomized, Single-Arm Trial. Oraee-Yazdani, S., Tavanaei, R., Rezaee-Naserabad, SS., et al.[2023]

A study of 77 patients undergoing selective dorsal rhizotomy showed that motor responses to dorsal root stimulation are highly reproducible, with over 93% of dorsal roots showing consistent results between two stimulation trials.

The reliable intraoperative stimulation techniques help in accurately identifying abnormal rootlets, which is crucial for effectively reducing spasticity while preserving muscle strength.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reliability of intraoperative electrophysiological monitoring in selective posterior rhizotomy. Mittal, S., Farmer, JP., Poulin, C., et al.[2004]

In a study of 18 children with quadriplegic spastic cerebral palsy, selective dorsal rhizotomy (SDR) led to a significant decrease in spasticity across all muscle groups and a 3.2% improvement in overall motor function as measured by the Gross Motor Function Measure (GMFM).

Despite the reduction in spasticity, SDR did not prevent orthopedic complications, as indicated by unchanged hip migration and the need for further orthopedic surgeries in some children, highlighting the complexity of managing spastic cerebral palsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective dorsal rhizotomy in children with cerebral palsy. Results in 18 cases at one year postoperatively. Hodgkinson, I., Bérard, C., Jindrich, ML., et al.[2018]

Selective dorsal rhizotomy (SDR) is a safe surgical technique that effectively reduces spasticity and improves functional outcomes in children with spastic diplegia due to cerebral palsy, as indicated by various measures including the gross motor function measurement scale (GMFM).

Long-term studies show that SDR provides significant and lasting improvements in motor skills, strength, and daily activities, making it a valuable option for managing spasticity in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective dorsal rhizotomies in the treatment of spasticity related to cerebral palsy. Farmer, JP., Sabbagh, AJ.[2018]

Selective dorsal rhizotomy is an effective surgical procedure for reducing lower-extremity spasticity in children with cerebral palsy, and the authors present a modified technique that requires only a single-level laminectomy, which reduces operating time and postoperative pain.

In over 1500 patients treated since 1991, this modified procedure has shown to be well tolerated with a low complication rate, including only one case of cerebrospinal fluid leakage requiring repair.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical techniques of selective dorsal rhizotomy for spastic cerebral palsy. Technical note. Park, TS., Johnston, JM.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06070233?term=AREA%5BConditionSearch%5D(spinal%20cord%20injury)%20AND%20SEARCH%5BLocation%5D(AREA%5BLocationCountry%5DUnited%20States%20AND%20AREA%5BLocationState%5DOhio%20AND%20AREA%5BLocationCity%5DColumbus)%20AND%20AREA%5BOverallStatus%5D(RECRUITING)&rank=6

Radiosurgery Treatment for Spasticity Associated With ... This treatment is called "stereotactic radiosurgery dorsal rhizotomy." It uses very accurate beams of radiation to target certain nerves in the back to help ...

2. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/dmcn.16496

Outcomes of selective dorsal rhizotomy in ambulatory ... Selective dorsal rhizotomy (SDR) is an irreversible neurosurgical procedure which reduces spasticity in the lower limbs of children and young ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1878747923009911

The Evolution of Selective Dorsal Rhizotomy for ... Selective dorsal rhizotomy is a key technique in the surgical management of spasticity in patients with cerebral palsy.

4. withpower.com withpower.com/trial/phase-muscle-spasticity-9-2023-bd32d

Radiosurgery for Spasticity (SPASM Trial) Research shows that Selective Dorsal Rhizotomy (SDR), a component of the treatment, effectively reduces spasticity (muscle stiffness) in children with cerebral ...

5. pediatricsnationwide.org pediatricsnationwide.org/2024/11/11/selective-dorsal-rhizotomy-for-cerebral-palsy-significant-gains-in-mobility-and-reduction-in-spasticity-treatments/

Selective Dorsal Rhizotomy for Cerebral Palsy The study highlights motor improvements and a reduced need for spasticity treatments, emphasizing SDR's potential to enhance outcomes and ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7325386/

Stereotactic Dorsolateral Irradiation of Spinal Nerve Roots A novel treatment option was offered to provide relief from spasticity and pain: stereotactic image-guided irradiation delivered to the sensory root.