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Pathophysiology of Dystonia and Complex Regional Pain Syndrome

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03223623
Recruitment Status : Recruiting
First Posted : July 21, 2017
Last Update Posted : May 12, 2020
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )

Brief Summary:

Background:

Little is known about the problems in brain function in focal hand dystonia (FHD) or complex regional pain syndrome (CRPS) dystonia. It is unclear why some CRPS patients develop dystonia but others do not. Researchers want to learn which area of the brain is involved in CRPS dystonia compared with FHD.

Objectives:

To understand why people with CRPS develop dystonia, and if these reasons are different in people with FHD.

Eligibility:

Adults ages 18 - 70 with CRPS dystonia OR with CRPS without dystonia OR with FHD and Healthy volunteers of similar age.

Design:

Participants will be screened with physical exam, neurological exam, and medical history. They may give a urine sample and will answer questions.

Participants can have 4 - 5 outpatient visits or stay at the clinical center for approximately 5-6 days.

Participants will have MRI scans. They will lie on a table that slides in and out of a scanner that takes pictures of their brain. They will do small tasks or be asked to imagine things during the scanning.

Participants will have transcranial magnetic stimulation (TMS) sessions for a few hours, with breaks. A brief electrical current passing through a well insulated wire coil on the scalp creates a magnetic pulse. This affects brain activity. Participants may do small tasks during TMS.

Participants will have the electrical activity of their muscles measured during TMS sessions. Small sticky pads will be attached to their hands and arms.

Participants ability to feel 2 separate stimuli as different will be tested by using a weak electrical shock to their fingers. They will also be asked to feel small plastic domes with ridges, that may cause discomfort.


Condition or disease Intervention/treatment Phase
Dystonia Complex Regional Pain Syndromes Procedure: TMS Procedure: MRI Procedure: VASO Imaging Not Applicable

Detailed Description:

Objective:

Detailed evaluation of pathophysiology of Complex Regional Pain Syndrome (CRPS) dystonia compared to Focal Hand Dystonia (FHD) with focus on the involvement of the parietal area, and to investigate differences in cortical mapping in the sensory and motor cortices between FHD and healthy volunteers.

Study population:

The study will enroll patients with (FHD), CRPS dystonia, CRPS without dystonia and Healthy Volunteers (HVs).

Design:

Prospective study using MRI and Physiology experiments using EMG and TMS based protocols to evaluate the differences between the groups.

Outcome measures:

The evaluation using fMRI will be performed under 3 conditions; 1. Rest 2. Voluntary activity 3. Motor imagery task.

Outcome measures (fMRI based):

  • We will explore the differences in BOLD signal in the parietal lobe, in CRPS dystonia compared to FHD, in the different conditions. We will look for changes in the BOLD signal in the parietal sensorimotor integration area.
  • We will further explore the differential activation in CRPS dystonia vs CRPS without dystonia to identify any specific features inherent to patients with CRPS dystonia compared to CRPS alone.
  • We will use vascular occupancy imaging (VASO) to explore differences of detailed cortical mapping of neural structures between FHD and healthy volunteers.

The Physiology experiments aim to explore abnormalities and differences in the baseline motor cortical excitability between the groups and evaluated the influence of continuous Theta Burst Stimulation (cTBS) on these measures. We will study the influence of cTBS on the phenomenon Cortical Silent Period ( cSP) in CRPS dystonia and FHD.

We will also be studying the baseline Spatial and Temporal Discrimination (SDTs and TDTs), which are measures of sensory surround inhibition. TDT and SDT abnormalities have been noted to be endophenotypic of dystonia, however the comparative characteristics between FHD and CRPS dystonia are not known.

Physiology outcomes:

  • Baseline differential influences of PMv and IPL on motor cortical excitability and changes after cTBS of dIPL.
  • Baseline cortical Silent Period (cSP) in the involved and uninvolved limb in FHD and CRPS dystonia and the influence of cTBS on cSP between the groups in the involved limb.
  • The TDTs/ SDTs in both the involved and uninvolved limbs in FHD and CRPS dystonia compared to HVs.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Investigations of Pathophysiology of Dystonia and Complex Regional Pain Syndrome
Actual Study Start Date : December 12, 2017
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2021


Arm Intervention/treatment
Active Comparator: CRPS dystonia
adults with CRPS dystonia
Procedure: TMS
Single pulse TMS

Procedure: MRI
Session 1: High-resolution MRI for anatomical reference, and sequences included in the clinical scan protocol; Session 2: fMRI protocol will be conducted under 3 conditions. 1. Rest 2. Voluntary activity 3. Motor imagery task.

Active Comparator: CRPS without dystonia
adults with CRPS without dystonia
Procedure: TMS
Single pulse TMS

Procedure: MRI
Session 1: High-resolution MRI for anatomical reference, and sequences included in the clinical scan protocol; Session 2: fMRI protocol will be conducted under 3 conditions. 1. Rest 2. Voluntary activity 3. Motor imagery task.

Active Comparator: FHD
adults with Focal Hand Dystonia
Procedure: TMS
Single pulse TMS

Procedure: MRI
Session 1: High-resolution MRI for anatomical reference, and sequences included in the clinical scan protocol; Session 2: fMRI protocol will be conducted under 3 conditions. 1. Rest 2. Voluntary activity 3. Motor imagery task.

Procedure: VASO Imaging
Similar to MRI, but voluntary activity condition will involve 4 tasks: a. individual tapping of two fingers (index and little), b. individual tapping of four fingers (index, middle, ring, and little; no thumb) interspaced with rest periods, c. individual tapping of all five fingers (index, middle, ring, little, and thumb) interspaced with rest periods and d. Alternating grasping or retraction of a rubber ball interspaced with rest periods.

Placebo Comparator: Healthy Volunteer
adult healthy volunteers
Procedure: TMS
Single pulse TMS

Procedure: MRI
Session 1: High-resolution MRI for anatomical reference, and sequences included in the clinical scan protocol; Session 2: fMRI protocol will be conducted under 3 conditions. 1. Rest 2. Voluntary activity 3. Motor imagery task.

Procedure: VASO Imaging
Similar to MRI, but voluntary activity condition will involve 4 tasks: a. individual tapping of two fingers (index and little), b. individual tapping of four fingers (index, middle, ring, and little; no thumb) interspaced with rest periods, c. individual tapping of all five fingers (index, middle, ring, little, and thumb) interspaced with rest periods and d. Alternating grasping or retraction of a rubber ball interspaced with rest periods.




Primary Outcome Measures :
  1. explore the differences in BOLD signal in the parietal lobe, in CRPS dystonia compared to FHD, in the different conditions [ Time Frame: throughout ]
    We will look for changes in the BOLD signal in the parietal sensori-motor integration area.


Secondary Outcome Measures :
  1. TMS outcomes (continuous): differential influences of PMv and IPL on motor cortical excitability, changes after cTBS of dIPL, changes in the SI measures post TBS in FHD. [ Time Frame: Ongoing ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

Healthy research volunteers, adult patients with FHD, CRPS patients with dystonia involving at least one hand and CRPS patients without dystonia will be eligible for the study.

  • Age between 18 - 70 years.
  • Able to give informed consent.
  • Able to comply with all study procedures.
  • Subjects must be willing to abstain from alcohol for at least 48 hours prior to the study.
  • Adult patients with an established diagnosis of FHD.
  • Healthy volunteers will be healthy subjects without neurological or psychiatric disorders established by history and physical/neurological examination.
  • Adult CRPS patients, diagnosed based on the Budapest Clinical diagnostic criteria by an experienced Neurologist, with the presence of dystonia involving at least one hand.
  • Adult CRPS patients, diagnosed based on the Budapest Clinical diagnostic criteria by an experienced Neurologist, without the presence of dystonia in any limbs.
  • Patients receiving botulinum toxin injections will be evaluated after 3 months since their last injection.
  • All participants must be able to obtain an MRI (No contraindications per MRI safety checklist) which will be part of the initial evaluation.

EXCLUSION CRITERIA:

  • Self-reported consumption of >14 alcoholic drinks/week for a man and >7 alcoholic drinks/week for a woman.
  • Patients on daily chronic opioid or benzodiazepine use.
  • Patients treated with anticholinergics, who are not willing and/or unable to withhold taking them for 1 week prior and for the duration of the study participation.
  • Patients taking opioids and/or benzodiazepines on an as needed basis, who are not willing and/or unable to withhold taking them for 1 week or time interval equivalent to 5 half-lives (whichever is shorter) prior to study participation and for the days during study participation.
  • Abnormal findings on neurological examination including cognitive impairment, except diagnosis of interest (FHD, CRPS with/without dystonia) in patients.
  • History of or current brain tumor, stroke, head trauma with loss of consciousness, epilepsy or seizures.
  • Past or present medical history of (a) neurological disorders, such as stroke, movement disorders (other than dystonia in the patient group), ataxias, myopathies, myasthenia gravis, demyelinating diseases, alcoholism, drug dependence; (B) ventricular arrhythmias, renal and hepatic insufficiency, vascular headache, or carcinoid syndrome.
  • Subjects with Baclofen pumps and/or neuro stimulators for pain.
  • Current episode of major depression or any major psychiatric illness. Note: SSRI use is not exclusionary.
  • Pregnant or breastfeeding women. Aside from history obtained at the screening, pregnancy status in women with childbearing potential is also established by urine pregnancy testing no more than 24 hours before each MRI and TMS sessions.
  • Subjects who have contraindications to MRI:

    • You have metal in your body which would make having an MRI scan unsafe, such as pacemakers, stimulators, pumps, aneurysm clips, metallic prostheses, artificial heart valves, cochlear implants or shrapnel fragments, or if you were a welder or metal worker, since you may small metal fragments in the eye.
    • You are uncomfortable in small closed spaces (you have claustrophobia) so that you would feel uncomfortable in the MRI machine.
    • You are not able to lie comfortably on your back for approximately 2 hours.
  • Subjects who have contra-indications for TMS

    • You have a pacemaker, implanted pump, stimulator, cochlear implant or metal objects inside the eye or skull.
    • You have hearing loss (assessed by participant self-report or history).
    • You are pregnant

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03223623


Contacts
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Contact: Elaine P Considine, R.N. (301) 435-8518 considinee@ninds.nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010    prpl@cc.nih.gov   
Sponsors and Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
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Principal Investigator: Mark Hallett, M.D. National Institute of Neurological Disorders and Stroke (NINDS)
Additional Information:
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Responsible Party: National Institute of Neurological Disorders and Stroke (NINDS)
ClinicalTrials.gov Identifier: NCT03223623    
Other Study ID Numbers: 170126
17-N-0126
First Posted: July 21, 2017    Key Record Dates
Last Update Posted: May 12, 2020
Last Verified: May 8, 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) ):
Complex Regional Pain Syndrome
CRPS
Dystonia
Additional relevant MeSH terms:
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Dystonia
Dystonic Disorders
Complex Regional Pain Syndromes
Reflex Sympathetic Dystrophy
Syndrome
Somatoform Disorders
Disease
Pathologic Processes
Mental Disorders
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Movement Disorders
Central Nervous System Diseases
Autonomic Nervous System Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases