Parkinson DiseaseNCT00040196
How the Loss of Dopamine and Dopamine-Restoring Medicines Affect Movement Performance
An observational study of Parkinson Disease, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
This study has two purposes: 1) to understand the effect of a decline of dopamine in the brain during normal aging and in patients with Parkinson's disease, and 2) to investigate how medicines used to treat Parkinson's disease improve movement performance in patients. Read more about this study
- Who is it for?
- Ages 21 years and olderHealthy volunteers can take part
- Conditions the study is for
- Parkinson Disease
- How many people
- 133 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Jun 2002to 9 Jul 2009
- 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 21 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- We will only include PD patients with a stable clinical response to L-DOPA and DAergic agents.
- We will only recruit patients with early or mild-to-moderate PD (score on Hoehn \& Yahr scale 148 less than 3).
- To obtain a homogeneous group, the PD cohort will comprise only non-demented, non-depressed, with parkinsonian symptoms and signs primarily akineto-rigid.
- If resting tremor is present, only patients with mild or moderate tremor (UPDRS tremor ratings 1 or 2 in the right upper limb) will be included in the study.
- Our group of healthy volunteers will include the following age range: 21-30 years, 31-40 years, 41-50 years, 51-60 years, 61-70 years, and 70 years and over.
- Research subjects may be male or female and they must be right-handed.
- Pregnant women will not participate in the study.
- Research subjects will be asked to refrain from caffeine and nicotine for at least 12 hours and to abstain from alcohol at least 24 hours before the fMRI.
Who cannot join
- Subjects belonging to one of the following groups will be excluded from the study:
- Subjects with a familial history of PD.
- Patients with a marked resting tremor (score at the UPDRS scale above 3 in the right upper limb).
- Patients with a score at Hoehn \& Yahr scale equal or above 3.
- Patients with progressive neurological disorders other than PD.
- Subjects with cognitive impairment (i.e., score on Mattis scale below 123/144).
Show all 20Show fewer
- Subjects with significant mood disturbances (i.e., score on BDI scale above 10).
- Subjects with abnormal MRI findings at visual inspection (prominent normal variants such as mega cisterna or cavum septum pellucidum, signs of severe cortical or subcortical atrophy, brain tumors, vascular diseases, trauma or AVMs).
- Subjects with a history of significant medical disorders, or requiring chronic treatment with other drugs that cannot be stopped.
- Subjects with prior exposure to neuroleptic agents or drug use.
- Subjects with significant past and present history of hypertension, cardiovascular disease and diabetes mellitus.
- Subjects with severe orthopedic or rheumatologic pathology of the right upper limb.
- Subjects with past or present neuropsychiatric illness, head trauma with loss of consciousness, epilepsy, cerebro-vascular disease, past and present history of alcohol or substance abuse, including cigarettes, medical conditions that may alter cerebral functioning
- Subjects with cancer.
- Subjects who have pacemakers, aneurysm clips (metal clips on the wall of a large artery), metallic prostheses (including heart valves and cochlear implants) or shrapnel fragments.
- Subjects incapable of giving an informed consent.
- Subjects with a positive pregnancy test.
- Subjects with pre-existing eyes condition.
- Subjects who are unable to tolerate being off of antiparkinsonian medications for 12 hours.
- Children will be excluded from the study because PD is infrequent before age 30.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Dopaminergic Modulation of Cerebral Connectivity During Sequential Finger Movements
This study has two purposes: 1) to understand the effect of a decline of dopamine in the brain during normal aging and in patients with Parkinson's disease, and 2) to investigate how medicines used to treat Parkinson's disease improve movement performance in patients.
Patients with Parkinson's disease have difficulty performing precise finger movements, mainly because of a dramatic decrease of a substance called dopamine in parts of the brain. Medicines such as levodopa, which help restore dopamine levels, can greatly improve function; however, little is known about how these drugs work. In normal aging, dopamine decreases slightly in certain parts of the brain, but the importance of this decline is poorly understood. This study may provide new information about Parkinson's disease and normal aging that might lead to better treatment strategies.
Read more
Patients with mild to moderate Parkinson's disease and healthy volunteers 21 years of age and older may be eligible for this study. All participants must be right-handed. All candidates will be screened with a medical history and physical and neurological examinations, including memory tests and mood examination.
Brain function will be studied using functional magnetic resonance imaging (fMRI) study and positron emission tomography (PET). Participants may be asked to stop using medications that can affect the central nervous system, such as sleeping pills or drugs for depression or anxiety, for 1 week before each study visit. Patients with Parkinson's disease may also be asked to stop using antiparkinsonian medications at least 12 hours before each visit. In addition, all participants will be asked to abstain from alcoholic beverages at least 24 hours before the fMRI and PET scans, and from nicotine and caffeine for at least 12 hours before the scans.
Participants will have fMRI, which uses a strong magnetic field and radio waves to create images of the brain. The subject lies on a table in a tunnel-like cylinder (the scanner) for 1 to 2 hours, lying still for 5 to 15 minutes at a time. He or she can communicate with the technician or researcher at all times during the test through an intercom system. Scans will be done while the subject is at rest and while he or she is performing finger movements. The movements involve pushing five buttons on a box-each button every 3 seconds on average in a specific order. Patients with Parkinson's disease will be studied off- and then on- medications that restore the levels of levodopa in the brain.
Some participants may be asked to undergo a PET scan on a separate visit. A PET scanner is a doughnut-shaped machine similar in appearance to a CT (computed tomography) scanner. PET scans detect radioactivity used to provide information on brain activity. Before the test begins, subjects are given a dose of carbidopa-a medicine that increases the amount of levodopa in the brain. A catheter (thin, plastic tube) is then inserted into an arm or wrist vein, and a radioactive form of levodopa called 18Fluorodopa is injected through the catheter. A moldable plastic mask with large openings for eyes, nose, and mouth is placed on the face to help keep the head still during scanning. The total scan time is 2 hours or less.
Read the detailed description
Objective: In the central nervous system, short-term plasticity can be defined as a change in connection strength that is induced by receiving presynaptic inputs. Dopamine (DA), a neuromodulatory neurotransmitter, is believed to play a role in short-term plasticity. [18F]dopa positron emission tomography (PET) studies have shown progressive impairment of presynaptic dopaminergic (DAergic) function in both healthy elderly subjects (HES) and patients with Parkinson's disease (PD). Both PD and HES are characterized by a progressive decline in performance on some motor tasks and changes in activity in brain areas involved in motor control (including motor control by cognitive functions) as shown by functional imaging studies. However, little is known about the exact neurobiological mechanisms linking DAergic function, brain activity and motor (and cognitive) performances in PD and HES. In the present study, we hypothesize that impaired performance on some motor tasks in those subject groups is related to a dysfunction of task-specific functional connections between areas participating in motor control. In addition, the brain activation with fMRI across sessions and across subjects in the healthy group will be examined to investigate the reliability of the fMRI techniques.
Study population: We will study two groups of participants: one group of patients with mild-to-moderate PD and one group of healthy subjects.
Design: We will measure cerebral activity in baseline condition and during the execution of sequential finger movements using perfusion functional magnetic resonance imaging (fMRI) in the three subject groups. The reliability of fMRI data across sessions and across subjects in the healthy young group and brain activity in patients with PD will be studied "off" and then "on" medication.
Outcome measures: Imaging data will be compared in terms of both regional activity and effective connectivity using the statistical parametric mapping (SPM) software.
These experiments should lead to better understanding the pathophysiology of the mesencephalic DAergic system in human motor control and may lead to better treatment strategies in PD.
- Conditions
- Parkinson Disease
- Keywords
- Parkinson's Disease, Levodopa, Perfusion fMRI, Aging, Motor Control, PD, Healthy Volunteer, HV, Normal Control
- Medical subject headings
- Parkinson Disease
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2002 (estimated)
- Study start19 Jun 2002
- Primary completion9 Jul 2009
- Study completion9 Jul 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Parkinson DiseaseStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Enrolment
- 133 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00040196
- Sponsor's protocol ID
- 020216
- Other IDs
- 02-N-0216
- Status last verified
- 9 Jul 2009
- First submitted
- 21 Jun 2002
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Kupfermann I. Modulatory actions of neurotransmitters. Annu Rev Neurosci. 1979;2:447-65. doi: 10.1146/annurev.ne.02.030179.002311.
PubMed 44174Melamed E, Lavy S, Cooper G, Bentin S. Regional cerebral blood flow in parkinsonism. Measurement before and after levodopa. J Neurol Sci. 1978 Oct;38(3):391-7. doi: 10.1016/0022-510x(78)90144-2.
PubMed 731264Tedroff J, Pedersen M, Aquilonius SM, Hartvig P, Jacobsson G, Langstrom B. Levodopa-induced changes in synaptic dopamine in patients with Parkinson's disease as measured by [11C]raclopride displacement and PET. Neurology. 1996 May;46(5):1430-6. doi: 10.1212/wnl.46.5.1430.
PubMed 8628494
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dopaminergic Modulation of Cerebral Connectivity During Sequential Finger Movements
- ClinicalTrials.gov ID
- NCT00040196
- Acronym / sponsor ID
- 020216
- Conditions
- Parkinson Disease
- Keywords
- Parkinson's Disease, Levodopa, Perfusion fMRI, Aging, Motor Control, PD, Healthy Volunteer, HV
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 133 participants
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 19 Jun 2002
- Primary completion
- 9 Jul 2009 (actual)
- Study completion
- 9 Jul 2009 (actual)
- First posted
- 24 Jun 2002 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study has two purposes: 1) to understand the effect of a decline of dopamine in the brain during normal aging and in patients with Parkinson's disease, and 2) to investigate how medicines used to treat Parkinson's disease improve movement performance in patients.
Patients with Parkinson's disease have difficulty performing precise finger movements, mainly because of a dramatic decrease of a substance called dopamine in parts of the brain. Medicines such as levodopa, which help restore dopamine levels, can greatly improve function; however, little is known about how these drugs work. In normal aging, dopamine decreases slightly in certain parts of the brain, but the importance of this decline is poorly understood. This study may provide new information about Parkinson's disease and normal aging that might lead to better treatment strategies.
Patients with mild to moderate Parkinson's disease and healthy volunteers 21 years of age and older may be eligible for this study. All participants must be right-handed. All candidates will be screened with a medical history and physical and neurological examinations, including memory tests and mood examination.
Brain function will be studied using functional magnetic resonance imaging (fMRI) study and positron emission tomography (PET). Participants may be asked to stop using medications that can affect the central nervous system, such as sleeping pills or drugs for depression or anxiety, for 1 week before each study visit. Patients with Parkinson's disease may also be asked to stop using antiparkinsonian medications at least 12 hours before each visit. In addition, all participants will be asked to abstain from alcoholic beverages at least 24 hours before the fMRI and PET scans, and from nicotine and caffeine for at least 12 hours before the scans.
Participants will have fMRI, which uses a strong magnetic field and radio waves to create images of the brain. The subject lies on a table in a tunnel-like cylinder (the scanner) for 1 to 2 hours, lying still for 5 to 15 minutes at a time. He or she can communicate with the technician or researcher at all times during the test through an intercom system. Scans will be done while the subject is at rest and while he or she is performing finger movements. The movements involve pushing five buttons on a box-each button every 3 seconds on average in a specific order. Patients with Parkinson's disease will be studied off- and then on- medications that restore the levels of levodopa in the brain.
Some participants may be asked to undergo a PET scan on a separate visit. A PET scanner is a doughnut-shaped machine similar in appearance to a CT (computed tomography) scanner. PET scans detect radioactivity used to provide information on brain activity. Before the test begins, subjects are given a dose of carbidopa-a medicine that increases the amount of levodopa in the brain. A catheter (thin, plastic tube) is then inserted into an arm or wrist vein, and a radioactive form of levodopa called 18Fluorodopa is injected through the catheter. A moldable plastic mask with large openings for eyes, nose, and mouth is placed on the face to help keep the head still during scanning. The total scan time is 2 hours or less.
Detailed description
Objective: In the central nervous system, short-term plasticity can be defined as a change in connection strength that is induced by receiving presynaptic inputs. Dopamine (DA), a neuromodulatory neurotransmitter, is believed to play a role in short-term plasticity. [18F]dopa positron emission tomography (PET) studies have shown progressive impairment of presynaptic dopaminergic (DAergic) function in both healthy elderly subjects (HES) and patients with Parkinson's disease (PD). Both PD and HES are characterized by a progressive decline in performance on some motor tasks and changes in activity in brain areas involved in motor control (including motor control by cognitive functions) as shown by functional imaging studies. However, little is known about the exact neurobiological mechanisms linking DAergic function, brain activity and motor (and cognitive) performances in PD and HES. In the present study, we hypothesize that impaired performance on some motor tasks in those subject groups is related to a dysfunction of task-specific functional connections between areas participating in motor control. In addition, the brain activation with fMRI across sessions and across subjects in the healthy group will be examined to investigate the reliability of the fMRI techniques.
Study population: We will study two groups of participants: one group of patients with mild-to-moderate PD and one group of healthy subjects.
Design: We will measure cerebral activity in baseline condition and during the execution of sequential finger movements using perfusion functional magnetic resonance imaging (fMRI) in the three subject groups. The reliability of fMRI data across sessions and across subjects in the healthy young group and brain activity in patients with PD will be studied "off" and then "on" medication.
Outcome measures: Imaging data will be compared in terms of both regional activity and effective connectivity using the statistical parametric mapping (SPM) software.
These experiments should lead to better understanding the pathophysiology of the mesencephalic DAergic system in human motor control and may lead to better treatment strategies in PD.
Study design
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- We will only include PD patients with a stable clinical response to L-DOPA and DAergic agents.
- We will only recruit patients with early or mild-to-moderate PD (score on Hoehn \& Yahr scale 148 less than 3).
- To obtain a homogeneous group, the PD cohort will comprise only non-demented, non-depressed, with parkinsonian symptoms and signs primarily akineto-rigid.
- If resting tremor is present, only patients with mild or moderate tremor (UPDRS tremor ratings 1 or 2 in the right upper limb) will be included in the study.
- Our group of healthy volunteers will include the following age range: 21-30 years, 31-40 years, 41-50 years, 51-60 years, 61-70 years, and 70 years and over.
Key exclusion criteria (20 listed)
- Subjects with a familial history of PD.
- Patients with a marked resting tremor (score at the UPDRS scale above 3 in the right upper limb).
- Patients with a score at Hoehn \& Yahr scale equal or above 3.
- Patients with progressive neurological disorders other than PD.
- Subjects with cognitive impairment (i.e., score on Mattis scale below 123/144).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 44174Kupfermann I. Modulatory actions of neurotransmitters. Annu Rev Neurosci. 1979;2:447-65. doi: 10.1146/annurev.ne.02.030179.002311.
- Background: PubMed 731264Melamed E, Lavy S, Cooper G, Bentin S. Regional cerebral blood flow in parkinsonism. Measurement before and after levodopa. J Neurol Sci. 1978 Oct;38(3):391-7. doi: 10.1016/0022-510x(78)90144-2.
- Background: PubMed 8628494Tedroff J, Pedersen M, Aquilonius SM, Hartvig P, Jacobsson G, Langstrom B. Levodopa-induced changes in synaptic dopamine in patients with Parkinson's disease as measured by [11C]raclopride displacement and PET. Neurology. 1996 May;46(5):1430-6. doi: 10.1212/wnl.46.5.1430.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Parkinson Disease, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
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 8 inclusion and 20 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: finished, as of the sponsor's last update on 2 Jul 2017. 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 United States. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00040196, which also lists 3 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 2 Jul 2017.