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

Trial Summary

What is the purpose of this trial?

Combined Phase II/III, multi-center, prospective, single-blinded trial. Ten (10) patients with essential tremor who previously underwent successful and uncomplicated GK thalamotomy for essential tremor will undergo a contralateral treatment. The incidence of side effects will be determined at 3 months postoperatively, graded per the CTCAE v5 and analyzed by a data safety monitoring board. Upon successful review, this Phase II trial will be converted to a Phase III trial of utility that will enrol 40 additional patients. The primary outcome will be the change in QUEST score at 12 months postoperatively, as well as a patient-reported assessment of Health Utility. Secondary outcomes will include objective tremor, gait and speech assessments (filmed and scored by blinded evaluators), as well as quality of life questionnaires and adverse events questionnaires. Outcomes will be assessed at baseline, as well as 3, 6, 12, 24 and 36 months post-operatively.

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 data supports the effectiveness of the treatment Gamma Knife VIM thalamotomy for essential tremor?

Research shows that Gamma Knife thalamotomy is effective in treating tremors associated with conditions like Parkinson's Disease, Essential Tremor, and Multiple Sclerosis. Studies have reported that many patients experience significant relief from tremors after undergoing this treatment. ^{1 2 3 4 5}

Is Gamma Knife thalamotomy safe for humans?

Gamma Knife thalamotomy is generally considered safe, with most complications being mild, such as numbness or temporary weakness. However, rare severe complications like difficulty swallowing and even death have been reported, highlighting the importance of long-term follow-up. ^{1 5 6 7 8}

How is Gamma Knife treatment different from other treatments for essential tremor?

Gamma Knife treatment for essential tremor is unique because it uses focused radiation to target specific brain areas without the need for open surgery, making it a less invasive option. It is particularly useful for patients who cannot undergo traditional surgical methods. ^{1 2 3 5 9}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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 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]

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 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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Gamma Knife thalamotomy for treatment of essential tremor: long-term results. [2010]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Gamma Knife thalamotomy and pallidotomy in patients with movement disorders: preliminary results. [2018]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Movement disorders. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Gamma knife thalamotomy for multiple sclerosis tremor. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Gamma Knife Thalamotomy for Essential Tremor: A Retrospective Analysis. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

A prospective single-blind study of Gamma Knife thalamotomy for tremor. [2023]

7. Ireland pubmed.ncbi.nlm.nih.gov

Gamma knife stereotactic radiosurgical thalamotomy for intractable tremor: a systematic review of the literature. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Emergence of complex, involuntary movements after gamma knife radiosurgery for essential tremor. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Gamma Knife thalamotomy for essential tremor. [2008]