Gamma Knife Treatment for Essential Tremor

(BEST-GK Trial)

Recruiting at 1 trial location

Overseen By Christian Iorio-Morin

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Université de Sherbrooke

Disqualifiers: Gait impairment, Speech impairment, others

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

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: Immediate procedure

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of Gamma Knife thalamotomy, a precise brain surgery, for individuals with essential tremor, a condition causing uncontrollable shaking. It targets those who previously received successful treatment on one side of the brain and now require treatment on the other side due to tremors affecting daily life. Researchers aim to determine if this treatment improves quality of life, reduces tremors, and minimizes side effects. If the initial phase proves successful, more participants may join to further test its effectiveness. Participants must have undergone a previous Gamma Knife treatment and experience a tremor that significantly impacts their life. As a Phase 2, Phase 3 trial, this study focuses on assessing the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking 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.

What prior data suggests that Gamma Knife VIM thalamotomy is safe for treating essential tremor?

Research has shown that Gamma Knife thalamotomy is generally well-tolerated by people with essential tremor. A review of studies found that using the Gamma Knife for this condition is promising in terms of safety. Most patients experienced significant improvement in their tremors without serious side effects.

One study found that patients who underwent the procedure on both sides of the brain did not report any problems or difficulties after their first treatment. This suggests the procedure can be safe when performed bilaterally.

In one case, a patient experienced a temporary issue, but it resolved. Overall, these findings suggest that Gamma Knife thalamotomy is safe for many patients, with most experiencing positive effects on their tremors. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Gamma Knife VIM thalamotomy is unique because it offers a non-invasive approach to treating essential tremor, a condition often managed by medications like propranolol or primidone, or invasive procedures like deep brain stimulation. Unlike these standard options, the Gamma Knife uses precise radiation to target the VIM area of the thalamus, potentially reducing tremors without the need for surgical incisions. This method minimizes recovery time and reduces the risk of complications associated with traditional surgery, which is why researchers are eager to see how effective it can be in managing essential tremor.

What evidence suggests that Gamma Knife VIM thalamotomy might be an effective treatment for essential tremor?

Research has shown that Gamma Knife VIM thalamotomy, which participants in this trial will undergo, is a safe and effective treatment for essential tremor (ET). In studies, many patients experienced a significant reduction in their tremors, with some even achieving complete cessation. This treatment uses focused radiation to target and disrupt the brain area causing the tremors, eliminating the need for open surgery. While some patients might experience minor side effects, these are usually temporary. Overall, Gamma Knife thalamotomy offers a promising option for people with essential tremor seeking symptom relief. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with essential tremor or ET plus, diagnosed by a specialist. They must have had successful Gamma Knife thalamotomy on one side over a year ago and now seek treatment for the other side due to life quality impact.

Inclusion Criteria

My untreated side's tremor significantly affects my quality of life.

I had a GK thalamotomy procedure over a year ago.

I had a GK thalamotomy procedure more than a year ago.

Exclusion Criteria

My doctor has advised against me joining the trial.

I have trouble walking or balancing, and may use a wheelchair, walker, or cane.

I have trouble being understood when I speak.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo a contralateral thalamotomy using Gamma Knife

Immediate procedure

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

36 months

Regular assessments at 3, 6, 12, 24, and 36 months post-operatively

Extension

Potential continuation of monitoring for long-term outcomes

Beyond 36 months

What Are the Treatments Tested in This Trial?

Interventions

• Gamma Knife VIM thalamotomy

Trial Overview

The study tests Gamma Knife VIM thalamotomy's effectiveness and safety in treating the opposite brain side in patients who've already undergone this procedure. It starts as Phase II with ten patients, potentially expanding to Phase III with forty more after safety review.

How Is the Trial Designed?

Group I: Treatment group Experimental Treatment 1 Intervention

Participants will undergo a thalamotomy contralateral to their previous treatment with Gamma Knife using a frame-based, Gamma Knife Perfexion or Icon unit (Elekta, Stockholm, Sweden).

Gamma Knife VIM thalamotomy is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Gamma Knife VIM thalamotomy for:

• Essential tremor

Approved in United States as Gamma Knife VIM thalamotomy for:

• Essential tremor

Approved in Canada as Gamma Knife VIM thalamotomy for:

• Essential tremor

Approved in Japan as Gamma Knife VIM thalamotomy for:

• Essential tremor

Who Is Running the Clinical Trial?

Université de Sherbrooke

Lead Sponsor

Trials

317

Recruited

79,300+

University Health Network, Toronto

Collaborator

Trials

1,555

Recruited

526,000+

Published Research Related to This Trial

Gamma Knife thalamotomy (GKT) significantly reduced tremor severity in 26 patients with medically refractory essential tremor, with a mean tremor score improving from 3.7 to 1.7 after treatment, indicating its efficacy as a therapeutic option.

The procedure was found to be safe, with 69% of patients showing improvement in both tremor and handwriting scores, although there were some complications, including mild hemiparesis and speech impairment in a few patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gamma Knife thalamotomy for essential tremor. Kondziolka, D., Ong, JG., Lee, JY., et al.[2008]

The Leksell Gamma Knife is a safe and effective method for performing thalamotomy and pallidotomy in older patients with Parkinson's disease and related movement disorders, as shown in a preliminary report.

In the study, 2 out of 3 patients with severe intention tremor and 4 out of 7 patients with Parkinson's tremor experienced symptom relief from thalamotomy, while 4 out of 8 patients showed significant improvement in rigidity after pallidotomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gamma Knife thalamotomy and pallidotomy in patients with movement disorders: preliminary results. Rand, RW., Jacques, DB., Melbye, RW., et al.[2018]

Unilateral Gamma Knife thalamotomy (GKT) significantly improved upper limb tremor scores by 54.2% and daily living activities by 72.2% in 50 patients with severe refractory tremor, demonstrating its efficacy as a treatment option.

The procedure was found to be safe, with only one patient experiencing a transient side effect of hemiparesis due to edema, indicating that serious complications are rare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective single-blind study of Gamma Knife thalamotomy for tremor. Witjas, T., Carron, R., Krack, P., et al.[2023]

Gamma Knife thalamotomy has been proven effective over 30 years for treating tremors associated with Parkinson's Disease, Essential Tremor, and Multiple Sclerosis.

Despite its effectiveness, Gamma Knife pallidotomy has not gained widespread acceptance in the medical community.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Movement disorders. Ganz, JC.[2022]

Gamma knife thalamotomy significantly improved essential tremor symptoms in 27 patients, with an average improvement of over 50% in tremor, handwriting, and drawing scores after a follow-up of about 32.5 months.

Despite its efficacy, the procedure carries risks, with 6 patients experiencing adverse effects and 2 serious complications, highlighting the need for careful treatment planning to enhance safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gamma Knife Thalamotomy for Essential Tremor: A Retrospective Analysis. Horisawa, S., Hayashi, M., Tamura, N., et al.[2023]

Gamma knife stereotactic radiosurgical thalamotomy is a safe and well-tolerated treatment option for patients with intractable tremor who have not responded to medical therapy and are not surgical candidates, based on a systematic review of available literature.

While complications can occur, they are generally mild and include issues like contralateral numbness and transient hemiparesis, with severe complications being rare; this suggests that the procedure has a favorable safety profile when using doses between 130 to 150 Gy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gamma knife stereotactic radiosurgical thalamotomy for intractable tremor: a systematic review of the literature. Campbell, AM., Glover, J., Chiang, VL., et al.[2022]

A total of 172 patients underwent VIM thalamotomy using the Leksell Gamma Knife, resulting in significant reductions in tremor scores for writing and drawing, indicating its effectiveness in treating essential tremor (ET).

While the procedure is generally safe, 6.9% of patients experienced neurological side effects, with some being permanent, highlighting the importance of careful patient selection and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gamma Knife thalamotomy for treatment of essential tremor: long-term results. Young, RF., Li, F., Vermeulen, S., et al.[2010]

Gamma knife radiosurgery targeting the vim nucleus of the thalamus has been shown to effectively reduce tremors in patients with multiple sclerosis, with all six patients in the study experiencing improvement after a median latency of 2.5 months.

This minimally invasive procedure resulted in significant tremor amplitude reduction and functional improvement in four patients, with only one case of transient hemiparesis, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gamma knife thalamotomy for multiple sclerosis tremor. Mathieu, D., Kondziolka, D., Niranjan, A., et al.[2022]

Gamma knife radiosurgery is typically viewed as a safer option compared to traditional surgical methods like pallidotomy or thalamotomy for treating conditions like essential tremor.

However, this case study of a 59-year-old patient highlights that complications can still arise, as the patient developed a complex movement disorder after the procedure, emphasizing the importance of long-term follow-up to assess potential risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emergence of complex, involuntary movements after gamma knife radiosurgery for essential tremor. Siderowf, A., Gollump, SM., Stern, MB., et al.[2019]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/19895197/

Gamma Knife Thalamotomy for Treatment of Essential ...

Conclusions: A VIM thalamotomy with the Leksell GK offers a safe and effective alternative for surgical treatment of ET. It is particularly applicable to ...

2.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S1878875023003285

Gamma Knife Thalamotomy for Essential Tremor

Numerous studies on GK use in ET treatment have reported more varied responses and complication rates. Methods. Data from 27 patients with ET who underwent GK ...

3.

neurology.org

neurology.org/doi/10.1212/WNL.55.3.443

Functional outcomes after gamma knife thalamotomy for ...

Six of eight ET patients had complete tremor arrest, and the violent action tremor in all three patients with MS was improved. One patient developed transient ...

4.

elekta.com

elekta.com/medical-affairs/case-studies/case-study-bilateral-thalamotomy-with-leksell-gamma-knife-for-essential-tremor/

Bilateral Thalamotomy Leksell Gamma Knife | Case Study

Bilateral radiosurgery is safe in selected patients who present with no complications or impairments in the neurophysiological tests after the first treatment.

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10553193/

A Systematic Review Comparing Focused Ultrasound ...

Our systematic review found similar efficacy between FUS-T and SRS-T for ET, with trend toward higher efficacy yet greater adverse event incidence with FUS-T.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6581115/

Outcomes from stereotactic surgery for essential tremor - PMC

Overall, bilateral Vim DBS demonstrated more improvement in tremor reduction since both upper extremities were treated (range, 66%–78%). Several ...

7.

nature.com

nature.com/articles/s41598-024-52410-y

Dynamic functional changes upon thalamotomy in ... - Nature

Our results show that left Vim functional dynamics directly relates to upper limb tremor lowering upon intervention, while morphometry instead has a supporting ...