(I) Investigating the role of the cholinergic system and CBGTC-loop in the pathophysiology of CD, related to both motor and NMS; (II) Finding a biomarker for DBS efficacy in CD, including motor and NMS.
ID
Source
Brief title
Condition
- Movement disorders (incl parkinsonism)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameters are:
- The difference in [18F]FEOBV PET binding between CD patients and controls,
and its relation to motor- and NMS.
- The difference in intermuscular coherence between CD patients and controls,
and its relation to motor- and NMS.
Secondary outcome
The secondary endpoint of this study is the intermuscular coherence (pre- and
post-DBS) and cholinergic binding (only pre-DBS), and whether pre-operative
measurements are predictive for the effect of DBS on motor- and NMS.
Background summary
Cervical dystonia (CD) is a complex hyperkinetic movement disorder
characterized by abnormal movements and postures of the head and neck, as well
as a wide range of non-motor symptoms (NMS). The exact pathophysiology is still
unknown. Based on electrophysiological and functional imaging studies, it is
hypothesized to be caused by dysfunctional neuronal networks including the
basal ganglia, thalamus, cerebellum and cortices (CBGTC-loop). The activity of
this network can be investigated by intermuscular coherence, quantified through
electromyography (EMG). In this network, an abnormal function of acetylcholine
is hypothesized. The anticholinergic drug trihexyfenidyl is one of the only
effective drugs for dystonia, and in combination with the cognitive deficits in
dystonia patients, this points towards cholinergic dysfunction as a possible
factor in the pathofysiology of the disease.
Deep brain stimulation (DBS) of the globus pallidus interna (GPi) can be
considered in CD patients who are refractory to medical treatment, especially
botulinum toxin injections. However, there are still challenges for DBS. For
instance, DBS is not effective in all patients and the time required to observe
the stimulation effect can take months. To optimize therapy and select suitable
candidates for DBS treatment, a biomarker to indicate the expected response in
individual patients is yet to be defined.
In the present project we aim to increase knowledge on the pathophysiology of
CD, by investigating the CBGTC-loop and the activity of the cholinergic system
in CD patients. Next, we want to use this to develop a biomarker for DBS
efficacy in CD including motor- and NMS.
Study objective
(I) Investigating the role of the cholinergic system and CBGTC-loop in the
pathophysiology of CD, related to both motor and NMS;
(II) Finding a biomarker for DBS efficacy in CD, including motor and NMS.
Study design
This study is a single center prospective case-control study.
Study burden and risks
Burden: Patients will undergo DBS surgery as part of regular care. As part of
this regular care and before surgery (t=0), motor symptoms and NMS will be
assessed, as well as a general interview about medication use and medical
history. Also, an anatomical MRI and neuropsychological investigation will be
performed, as well as a videotaped motor examination.
In addition to this, we will send the patients four short questionnaires about
psychiatric symptoms, fatigue and quality of life which can be filled in at
home. During an additional visit, we will perform EMG-recordings to record
intermuscular coherence and perform a cholinergic PET-scan.
After twelve months (t=1), we will perform the motor- and non-motor
examinations once more. For the study we will additionally repeat
EMG-recordings and the questionnaires.
The controls will be tested at the same time points and this will consist of
the non-motor questionnaires, a shortened neuropsychological investigation,
EMG-recordings, an anatomical MRI scan with gadolinium contrast and one
cholinergic PET-scan.
Risks: The risks involved in the measurements of clinical characteristics and
intermuscular coherence are considered to be minimal. The PET scan will result
in a radiation dose of 6,1mSv per scan. According to the recommendations from
the International Commission of Radiological Protection (ICRP) a dose of
1-10mSv in one year for volunteers for biomedical research falls in a moderate
risk category (ICRP publication 103.2007). With one scan per year, participants
receive 6,1 mSv and therefore we are our study falls into this moderate risk
category. The MRI scan does not provide radiation risk, the only burden and
associated risk is the injection of contrast fluid (gadolinium).
Hanzeplein 1
Groningen 9700RB
NL
Hanzeplein 1
Groningen 9700RB
NL
Listed location countries
Age
Inclusion criteria
In order to participate in this study, CD patients must meet the following
criteria:
• Patients with a clinically confirmed diagnosis of idiopathic CD and age >= 18
years;
• A life expectancy of at least one year after surgery;
• For the patients in the EMG-part: DBS indication approved by the DBS team of
the patients hospital.
The inclusion criteria for the controls are:
• Age- and gender match to the participating patients;
• Life expectancy of at least one year after inclusion in the study;
• Age >= 18 years.
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in this study.
CD patients and controls:
• Relevant neurological conditions other than CD;
• Previous brain surgery;
• Impossibility to stop anticholinergic medication;
• Pregnancy or breast feeding;
• Exhibition to a radiation dose for medical research, exceeding the maximum
annual dose;
• Contra-indication for MRI scanning (MR incompatible implants, risk of metal
particles in the eyes, tattoos containing red pigments, sensitivity to contrast
fluid);
• Claustrophobia.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL78606.042.21 |