Botulinum Toxin + Isometric Exercises for Scoliosis

Overseen By Loren M Fishman, MD

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Manhattan Physical Medicine and Rehabilitation, LLP

Disqualifiers: Neuromuscular disease, Genetic abnormalities, Pregnancy, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 3 months

42 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a specific yoga-like exercise, combined with botulinum toxin injections, can reduce spinal curves in teenagers with adolescent idiopathic lumbar scoliosis. Previous studies have shown that the yoga pose alone can reverse scoliosis, and botulinum toxin is already approved for teens, but no one has tested them together until now. Researchers will divide participants into different groups to compare the effects of the treatments. Teenagers with scoliosis and a curve between 25 and 45 degrees who are willing to do daily yoga poses might be a good fit for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to innovative scoliosis treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that botulinum toxin type A is safe for teenagers. It is effective and generally well-tolerated for conditions like muscle stiffness in children as young as two years old. Some patients might develop antibodies that reduce the treatment's effectiveness over time, but serious side effects are rare.

Studies suggest that isometric yoga-like exercises are safe and can help with scoliosis. Research indicates these exercises can reduce spinal curves without significant risks. Both treatments have been studied separately and shown to be safe, but this trial is the first to test them together. While the FDA has already approved botulinum toxin for teenagers, the safety of using both treatments together remains under study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for scoliosis because they explore a unique combination of botulinum toxin type A and isometric yoga-like exercises. Unlike standard treatments, which often involve braces or surgery, this approach aims to relax and strengthen muscles to correct spinal curvature. Botulinum toxin type A potentially helps by relaxing overactive muscles, while the isometric exercises might enhance muscle strength and support. This dual approach could offer a less invasive option with promising results for managing scoliosis.

What evidence suggests that this trial's treatments could be effective for scoliosis?

Research shows that botulinum toxin type A can help with muscle imbalances in people with scoliosis. One study found it reduced muscle overactivity, which might benefit scoliosis patients. In this trial, some participants will receive botulinum toxin type A injections. Additionally, isometric maneuvers, exercises similar to yoga, have shown promise in reducing scoliosis curves. Previous studies reported improvements of 23.7% in the lower back (lumbar) and 27.6% in the upper back (thoracic). In this trial, other participants will engage in isometric yoga-like exercises. Although no studies have combined these treatments yet, each has shown positive results independently. ^{6 7 8 9 10}

Who Is on the Research Team?

Loren M Fishman

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

This trial is for teens aged 14-18 with adolescent idiopathic lumbar scoliosis, having a spinal curve between 25 and 45 degrees. They must be willing to do daily yoga-like exercises and have not been treated with botulinum toxin before. Participants need consent from a guardian, recent spine X-rays, and if female and sexually active, a negative pregnancy test.

Inclusion Criteria

My spine curve is between 25 and 45 degrees.

Stated willingness to do the yoga and yoga-like poses daily

Written, signed consent by patient and parent/guardian

Exclusion Criteria

I have a genetic condition affecting my limbs or metabolism.

I am not pregnant and can undergo X-rays or exert myself for a short time without major issues.

I have a condition like cerebral palsy, myopathy, or have had a stroke.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive isometric yoga-like exercises and botulinum injections or placebo for 3 months

3 months

Daily exercises, 1 injection visit

Crossover Treatment

Placebo group receives the actual yoga pose and botulinum injections

3 months

1 injection visit, daily exercises

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

2 X-ray visits at 3 weeks and 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Botulinum toxin type A
• Isometric Yoga-like exercise
• Placebo

Trial Overview The study tests the combination of Incobotulinumtoxin A injections (a type of Botulinum toxin approved for teenagers) and special yoga-like isometric exercises to see if they can reduce spinal curvature in adolescents with idiopathic lumbar scoliosis more effectively than previous methods.

How Is the Trial Designed?

Group I: Crossover Active Control 2 Interventions

After the three months, Arm I and Arm II patients will be given botulinum injections, and Group I will be given the proper yoga-like exercise. These two arms will constitute a further comparator with their own performances in the first 3 months of the study.

Group II: Group III: True isometric exercise, botulinum injection Active Control 2 Interventions

Group III: Isometric yoga-like exercise, botulinum injection given

Group III: Group II Isometric yoga-like exercise, placebo injection given Placebo Group 1 Intervention

Group II isometric yoga-like exercise, injection of preservative-free normal saline.

Group IV: Group I: Placebo isometric measure, no injection Placebo Group 1 Intervention

Group I: no isometric yoga-like exercise, no injection given.

Botulinum toxin type A is already approved in United States, European Union for the following indications:

Approved in United States as Xeomin for:

• Upper limb spasticity (excluding spasticity caused by cerebral palsy)
• Chronic sialorrhea

Approved in European Union as Xeomin for:

• Upper limb spasticity
• Chronic sialorrhea
• Blepharospasm
• Cervical dystonia

Who Is Running the Clinical Trial?

Manhattan Physical Medicine and Rehabilitation, LLP

Lead Sponsor

Trials

4

Recruited

1,100+

Published Research Related to This Trial

Botulinum toxin (BT) is effectively used to treat muscle hyperactivity and gland overactivity, and its potential for treating non-muscular pain conditions is currently being researched.

There are significant differences among various BT products in terms of potency, formulation, and storage, indicating that they are not interchangeable and should be used with caution in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacology of botulinum toxin drugs]. Dressler, D.[2021]

IncobotulinumtoxinA (Xeomin) has been shown to be effective and well-tolerated for treating neurological conditions like blepharospasm, cervical dystonia, and post-stroke spasticity, based on randomized controlled trials lasting up to 89 weeks.

The safety profile of incobotulinumtoxinA is favorable, with mild to moderate adverse events such as eyelid ptosis and dry eye, and it has demonstrated therapeutic equivalence to another formulation, onabotulinumtoxinA, in treating blepharospasm and cervical dystonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and pharmacological properties of incobotulinumtoxinA and its use in neurological disorders. Jost, WH., Benecke, R., Hauschke, D., et al.[2018]

Incobotulinumtoxin-A is a cost-effective treatment for blepharospasm and cervical dystonia compared to onabotulinumtoxin-A, with incremental costs per quality-adjusted life-year of A$ 25,588 and A$ 23,794, respectively, based on a 5-year Markov model analysis.

The flexible treatment intervals for incobotulinumtoxin-A allow for better symptom management, resulting in patients experiencing fewer weeks of symptoms compared to the fixed 12-week intervals required for onabotulinumtoxin-A.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness of Incobotulinumtoxin-A with Flexible Treatment Intervals Compared to Onabotulinumtoxin-A in the Management of Blepharospasm and Cervical Dystonia. Tilden, D., Guarnieri, C.[2018]

In a study of 20 women with glabellar rhytides that did not respond well to Botox (BTX-A), treatment with Botulinum toxin type B (BTX-B) resulted in significant improvement, with peak effects observed one month after injection.

While BTX-B was effective for patients resistant to BTX-A, its effects lasted shorter (about 4 months) compared to the typical duration of BTX-A, and side effects were generally mild and temporary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Botulinum toxin type B for dynamic glabellar rhytides refractory to botulinum toxin type A. Alster, TS., Lupton, JR.[2019]

A single injection of botulinum toxin type A (BTxA) for treating bilateral trapezius hypertrophy in 30 women resulted in significant aesthetic improvements, with 53% of patients reporting 'very much improved' outcomes based on the Global Aesthetic Improvement Scale (GAIS).

The treatment was found to be safe, with only non-severe adverse events reported, and all patients experienced complete recovery within the follow-up period of 4 to 12 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Botulinum Toxin Type A Injection in Patients with Bilateral Trapezius Hypertrophy. Zhou, RR., Wu, HL., Zhang, XD., et al.[2022]

A systematic review of botulinum toxin treatments for cervical dystonia found that all serotype A and B products, except Prosigne, were effective compared to placebo, based on a comparison of clinical outcomes from multiple studies.

The analysis showed no significant efficacy differences among Dysport, Botox, Xeomin, and Myobloc at four weeks post-injection, and adverse events like dysphagia and injection site pain were not significantly higher in treatment groups compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A mixed treatment comparison to compare the efficacy and safety of botulinum toxin treatments for cervical dystonia. Han, Y., Stevens, AL., Dashtipour, K., et al.[2018]

A survey of Dysport injectors across 5 EU countries revealed that they generally follow product-labeling recommendations for administering botulinum neurotoxin type A, indicating a good understanding of its use in conditions like cervical dystonia and spasticity.

Despite this familiarity, some injectors occasionally deviate from the recommended practices, emphasizing the need for ongoing education about potential adverse events such as dysphagia and muscle weakness associated with Dysport treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dysport (botulinum toxin type A) in routine therapeutic usage: a telephone needs assessment survey of European physicians to evaluate current awareness and adherence to product labeling changes. Hubble, J., Schwab, J., Hubert, C., et al.[2022]

IncobotulinumtoxinA (Xeomin) has a longer shelf life and simpler storage requirements compared to traditional botulinum toxin products, indicating that it can remain stable without complexing proteins, which may also reduce the risk of immune reactions.

Clinical studies have demonstrated Xeomin's efficacy in treating conditions like cervical dystonia and blepharospasm, and it has shown a lower incidence of antibody-induced therapy failure, suggesting improved safety and effectiveness over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-year experience with incobotulinumtoxinA (Xeomin(®) ): the first botulinum toxin drug free of complexing proteins. Dressler, D.[2022]

Botulinum toxin type A (BTX-A) is a safe and effective treatment for cervical dystonia, helping to reduce involuntary muscle activity and improve neck movement and pain control.

To optimize treatment outcomes and minimize side effects, precise targeting of dystonic muscles during injections, using the lowest effective dose, and extending the time between treatments are recommended.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of botulinum toxin type A in the treatment of cervical dystonia. Comella, CL., Jankovic, J., Brin, MF.[2006]

Botulinum toxin A (Botox) injections in adult rabbit extraocular muscles (EOMs) led to a significant increase in satellite cell activation and myonuclear addition, indicating a remodeling response despite muscle paralysis.

The increase in MyoD-positive myonuclei and the presence of neonatal myosin heavy chain isoforms suggest that Botox may upregulate protein synthesis in EOMs, which helps explain why these muscles do not atrophy like other muscles after Botox treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Botulinum toxin treatment of extraocular muscles in rabbits results in increased myofiber remodeling. Ugalde, I., Christiansen, SP., McLoon, LK.[2022]

Injections of botulinum toxin into cervical muscles for treating spasmodic torticollis resulted in significant pain reduction and decreased muscle spasms for an average of 2 months.

Out of 36 patients, 25% reported at least a 50% improvement, with 44% experiencing 50-75% improvement, and 17% achieving over 75% improvement after several treatment sessions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of spasmodic torticollis by local injections of botulinum toxin]. Jedynak, CP., de Saint Victor, JF.[2011]

In a study involving 9 patients with adolescent idiopathic scoliosis (AIS), a single injection of botulinum toxin A into the psoas major muscle resulted in significant radiological improvements in spinal curvature, indicating the muscle's role in scoliosis pathology.

The treatment led to measurable corrective changes in both the thoracic and lumbar spine without any serious adverse events, suggesting that localized muscle paralysis can be a safe and effective intervention for AIS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of the paravertebral muscles in adolescent idiopathic scoliosis evaluated by temporary paralysis. Wong, C., Gosvig, K., Sonne-Holm, S.[2020]

Citations

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Incobotulinumtoxin A and Yoga-like Isometric Exercise in ... Three previous studies show that the yoga pose is effective for reversing scoliotic curves; Botulinum toxin has been approved by the FDA for teenagers. However, ...

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The Effect of Botulinum Toxin A Injections in the Spine ... Botulinum toxin A as a localized injection therapy (ITB) has been utilized to reduce spasticity and improve the motor dysfunction in cerebral ...

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1 of 8 RX.PA.005.MPC BOTOX, DYSPORT, MYOBLOC, ... Efficacy and safety of botulinum type A toxin (Dysport) in cervical dystonia: Results of the first US randomized, double-blind, placebo-controlled study.

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Botox Label - accessdata.fda.gov Formation of neutralizing antibodies to botulinum toxin type. A may reduce the effectiveness of BOTOX treatment by inactivating the biological activity of the ...

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Botulinum Toxin - StatPearls - NCBI Bookshelf Spasticity: Studies and clinical experience have established that the treatment is safe and effective in pediatric patients aged 2 to 17.

9. aetna.com aetna.com/cpb/medical/data/100_199/0113.html

Botulinum Toxin - Medical Clinical Policy Bulletins Ninety percent of spasmodic torticollis patients show some improvement of pain relief, head position, and disability, and botulinum toxin is now the treatment ...

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AHM Botulinum Toxin: Botox Clinical Indications OnabotulinumtoxinA (Botulinum Toxin Type A) may be indicated for 1 or more of the following: o Strabismus for deviations less that 50 prism diopters, ...