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TremorNCT04825119

Hyperkinetic Movements in Patients With Disease of Motor Neurons and Their Response to Treatment With Nusinersen

An observational study of Tremor and Involuntary Movements, run by University Medical Centre Ljubljana at 1 site in Slovenia.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Hyperkinetic movement disorders in patients with diseases of motor neurons will be studied. Patients with spinal muscular atrophy (SMA) and motor neuron disease patients will be studied. Involuntary movements will be video recorded and accelerometry with electromyography (EMG) will be recorded in a subset of patients. Read more about this study

Who is it for?
Any age
Conditions the study is for
Tremor, Involuntary Movements, SMA
What is being tested?
Nusinersen
Type of treatment
Injection or infusion
How many people
110 participants
Where
1 siteSlovenia
Study dates
1 Oct 2017to 30 Jul 2021
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Study population: Consecutive patients with ALS, PMA, or PLS followed in MND outpatient clinic will be included in the study. Consecutive SMA patients treated with Nusinersen and followed in MND outpatient clinic will be included.

Who may be able to join

  • Genetically proven SMA patients treated with Nusinersen
  • ''clinically definite ALS'' or ''clinically probable ALS'' or ''clinically probable ALS - laboratory supported'' according to the revised El Escorial diagnostic criteria or diagnosis of PMA or PLS

Who cannot join

  • No.

Trial locations and contacts

1 site in 1 country.

Maja Kojović, PhD, MD contact

1 522 4323 ext. +386

maja.kojovic@kclj.si

Katarina Vogelnik, MD contact

1 522 4323 ext. +386

vogelnik.kata@gmail.com

Slovenia1 site, 1 recruiting
  • University Medical Centre Ljubljana

    Ljubljana, 1000

    Maja Kojović, PhD, MD, 1 522 4323 ext. +386, maja.kojovic@kclj.si

    Recruiting

Other trials in Slovenia

About this study

Official title: Hyperkinetic Movements in Patients With Motor Neuron Disease and in Patients With Spinal Muscular Atrophy and Their Response to Treatment With Nusinersen

Hyperkinetic movement disorders in patients with diseases of motor neurons will be studied.

Patients with spinal muscular atrophy (SMA) and motor neuron disease patients will be studied. Involuntary movements will be video recorded and accelerometry with electromyography (EMG) will be recorded in a subset of patients. Hyperkinetic involuntary movements studied will be tremor and minipolymyoclonus. Tremor is defined as involuntary, rhythmic, oscillatory movements of a body part, and minipolymyoclonus are intermittent and irregular movements, with amplitudes sufficient to produce visible movements of the joints. Hyperkinetic movement disorders may be of central or peripheral origin and using accelerometry with EMG may help distinguish the two mechanisms. In patients with SMA the investigators will explore the effect of Nusinersen treatment on phenomenology and amplitude of tremor and minipolymyoclonus.

Read more

Aims: To explore the prevalence and phenomenology of hyperkinetic movement disorders in patients with MND and SMA and to study the underlying pathological mechanisms with the use of accelerometry and EMG. To explore the effect of Nusinersen treatment on phenomenology and amplitude of involuntary movements.

Hypotheses: Based on clinical observations the investigators believe it will proven that hyperkinetic movement disorders are common in patients with disease of motor neurons. The investigators hypothesize that hyperkinetic movement disorders in MND and SMA patients are of peripheral origin, being caused by uneven graduation of contraction in the wasted muscles with large motor units being active with no sufficient previous recruitment of small units to smooth contraction of large motor units. If tremor and minipolymyoclonus in SMA are due to the activation of enlarged motor units which are caused by reinnervation of muscle fibers, the treatment with Nusinersen will increase the amplitude of tremor and minipolymyoclonus.

Methods: Presence, quality, and regularity of hyperkinetic movement disorders will be defined using clinical examination, accelerometry and EMG. Hyperkinetic movements will be classified as minipolymyoclonus or tremor. In patients with SMA, the measurements will be repeated 6-12 months after initiation of treatment with Nusinersen.

Read the detailed description

Background: Minipolymyoclonus and tremor are frequently mentioned as part of the clinical picture of spinal muscular atrophy, but the precise mechanism of the occurrence of tremor and minipolymyoclonus in these patients remains unknown. In the 1970s it was suggested minipolymyoclonus and tremor are caused by reinnervation that follows denervation of muscle fibers in neuropathies. The investigators are not aware of any later or more systematic study on the frequency of minipolymyoclonus and tremor occurrence in SMA patients or its evolution during the disease course. Nusinersen, an antisense oligonucleotide, is a medicine registered for treating SMA. Nusinersen increases the production of the functional survival motor neuron protein by regulating gene expression and thus slows down or stops alpha-motor neuron degradation. MND is considered a disease of upper and lower motor neuron and movement disorders are not considered part of its typical clinical picture. Movement disorders are only reported in MND in association with extrapyramidal or cerebellar degeneration or dysfunction. Contrary to this, the investigators have encountered anecdotal evidence from a number of patients with otherwise typical MND who manifested involuntary jerks and tremor.

Aims: To explore the prevalence and phenomenology of hyperkinetic movement disorders in patients with SMA and MND, to explore the effect of Nusinersen treatment on phenomenology and amplitude of tremor and minipolymyoclonus, and to elucidate the underlying pathological mechanisms by using accelerometry and EMG.

Patients and inclusion/exclusion criteria: All genetically proven SMA patients who will be treated with Nusinersen and consecutive patients followed in MND outpatient clinic will be recruited. Patients with SMA type I, II, III, and IV and patients with ''clinically definite ALS'' or ''clinically probable ALS'' or ''clinically probable ALS - laboratory supported'' according to the revised El Escorial diagnostic criteria or with the diagnosis of PMA or PLS will be included. There will be no exclusion criteria.

Study protocol: All patients will be clinically examined and video-recorded. SMA patients will be examined and video-recorded for the second time 6-12 months after initiation of treatment with Nusinersen. The presence, quality, and regularity of involuntary movements will be evaluated while subjects will be sitting in a chair with hands resting in their lap (usual posture when examining rest tremor), during forward horizontal reach posture, and during finger to nose task. Based on regularity and distribution, hyperkinetic movements will be classified as minipolymyoclonus (MPMC) or tremor. Accelerometry with EMG will be recorded in a subset of patients with hyperkinetic movements.

Methods:

Accelerometry with electromyography: With accelerometry tremor (frequency and amplitude) in the subjects will be objectively evaluated. A triaxle accelerometer will be attached to the 3rd metacarpal bone bilaterally. Simultaneously EMG will be recorded. Bipolar Ag / AgCl surface EMG electrodes will be placed over the flexor carpi radialis and the extensor carpi radialis muscle bilaterally. Electromyography and accelerometry will be recorded while subjects will be sitting in an armchair/wheelchair or lying in a hospital bed (a) at rest position (b) with arms outstretched (postural condition) (c) at the postural condition with 500 g mass attached to the hand (weight loading) and (d) while performing a goal-directed task (action).

Statistical analysis: Clinical measures before and after Nusinersen treatment will be compared using two-related-samples T-test or repeated-measures ANOVA. To assess possible causative mechanisms (disease factors) that determine the presence of involuntary movements, separate multilevel binary logistic analyses will be performed.

Being tested
Nusinersen
Keywords
Tremor, Minipolymyoclonus, Nusinersen, SMA, MND, ALS
Medical subject headings
Tremor, Dyskinesias, Amyotrophic Lateral Sclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NusinersenDrug

    Also called Spinraza

    Patients with SMA who will be treated with nusinersen will be included.

Study groups in NCT04825119
Study groupRoleWhat they receive
MND patientsPatients with ''clinically definite ALS'' or ''clinically probable ALS'' or ''clinically probable ALS - laboratory supported'' according to the revised El Escorial diagnostic criteria or with the diagnosis of PMA or PLS will be included.
SMA patientsSMA patients type I, II, III, and IV will be included.
Receives: Drug: Nusinersen

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Prevalence of involuntary movements in patients with SMA before starting treatment with nusinersen

    All patients will be clinically examined and video-recorded before starting treatment with nusinersen. The presence of involuntary movements will be evaluated as present or not present while subjects will be sitting in a chair with hands resting in their lap (usual posture when examining rest tremor), during forward horizontal reach posture and during finger to nose task.

    Measured: Baseline (before starting nusinersen treatment)

  2. The effect of nusinersen on the prevalence of involuntary movements in patients with SMA

    All patients will be clinically examined and video-recorded 6-12 months after starting treatment with nusinersen. The presence of involuntary movements will be evaluated as present or not present while subjects will be sitting in a chair with hands resting in their lap (usual posture when examining rest tremor), during forward horizontal reach posture and during finger to nose task.

    Measured: 6-12 months after starting nusinersen

  3. Characteristics of involuntary movements in patients with SMA before starting treatment with nusinersen

    The quality and regularity of involuntary movements will be evaluated in the standard positons before starting treatment with nusinersen. Based on regularity and distribution, movements observed will be classified as minipolymyoclonus or tremor.

    Measured: Baseline (before starting nusinersen treatment)

  4. The effect of nusinersen on the characteristics of involuntary movements in patients with SMA

    The quality and regularity of involuntary movements will be evaluated in the standard positons 6-12 moths after starting treatment with nusinersen. Based on regularity and distribution, movements observed will be classified as minipolymyoclonus or tremor.

    Measured: 6-12 months after starting nusinersen

  5. Amplitude of involuntary movements in patients with SMA before starting treatment with nusinersen

    The quality and regularity of involuntary movements will be evaluated in the standard positons before starting treatment with nusinersen. Accelerometry with EMG will be recorded in all patients with hyperkinetic movements. Amplitude of involuntary movements will be graded on a scale from 0 to 3.

    Measured: Baseline (before starting nusinersen treatment)

  6. The effect of nusinersen on the amplitude of involuntary movements in patients with SMA

    The quality and regularity of involuntary movements will be evaluated in the standard positons 6-12 moths after starting treatment with nusinersen. Accelerometry with EMG will be recorded in all patients with hyperkinetic movements. Amplitude of involuntary movements will be graded on a scale from 0 to 3.

    Measured: 6-12 months after starting nusinersen

  7. Prevalence of involuntary movements in patients with MND

    Patients will be clinically examined by movement disorders experts and video-recorded. The presence of involuntary movements will be evaluated while subjects will be sitting in a chair with hands resting in their lap (usual posture when examining rest tremor), during forward horizontal reach posture and during finger to nose task.

    Measured: Day 1

  8. Characteristics of involuntary movements in patients with MND

    The quality and regularity of involuntary movements will be evaluated while subjects will be sitting in a chair with hands resting in their lap (usual posture when examining rest tremor), during forward horizontal reach posture and during finger to nose task. Based on regularity and distribution, hyperkinetic movements will be classified as minipolymyoclonus or tremor.

    Measured: Day 1

  9. Amplitude of involuntary movements in patients with MND

    In 10 patients accelerometry with electromyography will be recorded at standard positions.

    Measured: Day 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Apr 2021
  2. Study start1 Oct 2017
  3. Primary completion30 Jul 2021 (estimated)
  4. Study completion30 Jul 2021 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
110 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04825119
Sponsor's protocol ID
0120-293/2019/8/1
Status last verified
Mar 2021
First submitted
2 Mar 2021
Last updated
1 Apr 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Brooks BR, Miller RG, Swash M, Munsat TL; World Federation of Neurology Research Group on Motor Neuron Diseases. El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord. 2000 Dec;1(5):293-9. doi: 10.1080/146608200300079536. No abstract available.

    PubMed 11464847
  • Pupillo E, Bianchi E, Messina P, Chiveri L, Lunetta C, Corbo M, Filosto M, Lorusso L, Marin B, Mandrioli J, Riva N, Sasanelli F, Tremolizzo L, Beghi E; Eurals Consortium. Extrapyramidal and cognitive signs in amyotrophic lateral sclerosis: A population based cross-sectional study. Amyotroph Lateral Scler Frontotemporal Degener. 2015;16(5-6):324-30. doi: 10.3109/21678421.2015.1040028. Epub 2015 May 12.

    PubMed 25967544
  • Dawood AA, Moosa A. Hand and ECG tremor in spinal muscular atrophy. Arch Dis Child. 1983 May;58(5):376-8. doi: 10.1136/adc.58.5.376.

    PubMed 6859919
  • Wurster CD, Ludolph AC. Nusinersen for spinal muscular atrophy. Ther Adv Neurol Disord. 2018 Mar 13;11:1756285618754459. doi: 10.1177/1756285618754459. eCollection 2018. No abstract available.

    PubMed 29568328

Questions about this trial

What is this clinical trial studying?

An observational study of Tremor and Involuntary Movements, run by University Medical Centre Ljubljana at 1 site in Slovenia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 1 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Slovenia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Maja Kojović, PhD, MD (1 522 4323 ext. +386, maja.kojovic@kclj.si), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Prevalence of involuntary movements in patients with SMA before starting treatment with nusinersen (time frame: Baseline (before starting nusinersen treatment)). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04825119, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2021.

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