Parkinson's Disease With DementiaNCT01785628
The Impact of Pharmacological and Electric Modulation of NMDA Pathway on the Cognitive Flexibility and Volitional Movement Preparation in Patients With Parkinson's Disease
A study testing Sarcosine Capsule in people with Parkinson's Disease With Dementia, run by China Medical University Hospital at 1 site in Taiwan.
Trial summary
The project will investigate the effect of pharmacological and electric modulation of N-methyl-D-aspartate (NMDA) pathway on the cognitive flexibility and volitional movement preparation in patients with Parkinson's disease (PD). Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Parkinson's Disease With Dementia
- What is being tested?
- Sarcosine Capsule
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteTaiwan
- Study dates
- Aug 2010to Jul 2012
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
Who may be able to join
- The diagnosis of PD-D will be based on the criteria proposed by 2007 movement disorders PD-D task force. (Emre M et.al. Mov Disord 2007; 22:1689-1707)
Who cannot join
- Acute confusion due to systemic illnesses or drug intoxication.
- Major depression
- Features compatible with "Probable Vascular dementia.
- Patient who is pregnant.
Trial locations and contacts
1 site in 1 country.
About this study
The project will investigate the effect of pharmacological and electric modulation of N-methyl-D-aspartate (NMDA) pathway on the cognitive flexibility and volitional movement preparation in patients with Parkinson's disease (PD).
Read the detailed description
Sarcosine (also called N-methylglycine) is an endogenous GlyT-1 inhibitor. By blocking glycine uptake, sarcosine increases synaptic glycine concentration to enhance NMDA receptor function. NMDA receptor, a subtype of ionotropic glutamate receptors, serves important functions in the brain, including learning, memory, cognition, and neural plasticity under physiological conditions and contributes to neurodegeneration in pathophysiological processes. NMDA receptor represents collectively a group of heteromeric tetramers. Every NMDA receptor is a protein complex, typically composed of two NR1 subunits and two NR2 subunits that together form the NMDA receptor ion channel. It requires two receptor agonists (glutamate for the NR2 binding site and glycine for the NR1 binding site) to open the ion channel for NMDA receptor activation. Clinically, modulation through the NMDA-NR1-glycine site is preferred to avoid the excitotoxicity associated with the glutamate site activation.8 In addition, recent animal studies have shown that dopamine secretion can be enhanced by either blocking the striatal NR2 or by activation of the NMDA-receptor glycine site. In the project, we will focus on pharmacological enhancement of NMDA-glycine receptor function based on increasing synaptic glycine concentration by sarcosine administration to examine whether enhancing NMDA-glycine receptor activity can improve the neuropsychiatric symptoms, cognition and hopefully motor function in PD-D patients
- Conditions
- Parkinson's Disease With Dementia
- Being tested
- Sarcosine Capsule, Placebo Capsule
- Keywords
- Parkinson's disease, dementia, NMDA, event related potential, Bereitschaftspotential
- Medical subject headings
- Parkinson Disease, Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sarcosine CapsuleDietary supplement
Sarcosine is a glycine transporter-1 (GlyT-1) inhibitor. By blocking glycine uptake, sarcosine increases synaptic glycine concentration to enhance NMDA receptor function.
Placebo CapsuleDietary supplement
Placebo is dextrin composition.
| Study group | Role | What they receive |
|---|---|---|
| Sarcosine capsule | Experimental | Oral capsules of Sarcosine (0.5g capsule) 1g / bid for 8 weeks. Receives: Dietary Supplement: Sarcosine Capsule |
| Placebo capsule | Placebo comparator | Oral capsules of Placebo (Dextrin 0.5g capsule) 1g / bid for 8 weeks. Receives: Dietary Supplement: Placebo Capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Unified Parkinson's Disease Rating Scale (UPDRS) From Baseline to 8 Weeks.
Outcome is defined as change in total Unified Parkinson's Disease Rating Scale (UPDRS) between the baseline to 8 weeks. The UPDRS score has three parts, part I (Mentation, Behavior and Mood), Part II (Activities of Daily Living) and Part III (Motor Examination). Each consisting of questions answered on a 0-4 point scale. The minimum total score possible is 0 and the maximum total score possible is 176. Higher scores indicating more severe symptoms.
Measured: baseline to 8 weeks.
Secondary outcomes (7)
Change in Cognitive Abilities Screening Instrument (CASI) From Baseline to 8 Weeks.
The Cognitive Abilities Screening Instrument (CASI) has a score range of 0 to 100 and provides quantitative assessment on attention, concentration, orientation, short-term memory, long-term memory, language abilities, visual construction, list-generating fluency, abstraction, and judgment. With a higher score indicating Symptom improvement.
Measured: baseline to 8 weeks
Change in Clinical Dementia Rating (CDR) From Baseline to 8 Weeks.
The CDR is a 5-point scale used to characterize six domains of cognitive and functional performance applicable to Alzheimer disease and related dementias: Memory, Orientation, Judgment \& Problem Solving, Community Affairs, Home \& Hobbies, and Personal Care. With a higher score indicating more severe symptoms.
Measured: baseline to 8 weeks
Change in Neuropsychiatry Inventory (NPI) From Baseline to 8 Weeks.
The NPI scale has 12 domains: delusions, hallucinations, agitation, dysphoria, anxiety, apathy, irritability, euphoria, disinhibition, aberrant motor behavior, night-time behavior disturbances, and appetite and eating abnormalities. The total score ranges from 0 to 144, where the score for a domain is defined as the product of frequency (range: 1-4) and severity (range: 1-3). Each domain has a maximum score of 12 and with a higher score indicating more severe symptoms.
Measured: baseline to 8 weeks
Change in Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD) From Baseline to 8 Weeks.
The Behave-AD includes the assessment of symptoms and a global rating of caregiver distress. A total of 25 symptoms in 7 clusters are rated: paranoid and delusional ideation, hallucinations, aggressiveness, activity disturbances, diurnal rhythm disturbances, affective disturbances and anxieties, and phobias. Caregivers rate behavioral symptoms over the preceding 2 weeks on a 0 to 3 scale. The caregiver also determines a global assessment of caregiver distress on a scale of 0 to 3. The maximum score is 75 and with a higher score indicating more severe symptoms.
Measured: baseline to 8 weeks
Change in Hamilton Depression Rating Scale (HAM-D) From Baseline to 8 Weeks.
The HAM-D is a 21-item rating scaled which includes an emphasis on behavioral symptoms and somatic complaints that neglects self-reported feelings of distress; and an intermingling of frequency and intensity of symptoms. The total score ranges from 0 to 64: ten items are ranked on a scale from 0 to 4; 9 items are ranked 0 to 2; and 2 items are ranked 0 to 3. With a higher score indicating more severe symptoms.
Measured: baseline to 8 weeks
Change in Beck Depression Inventory-II (BDI-II) From Baseline to 8 Weeks.
The BDI-II is a 21-item self-report questionnaire assessing the current severity of depression symptoms. Each item is scored on a scale of 0 to 3 and the total score ranges from 0 to 63. With a higher score indicating more severe symptoms.
Measured: baseline to 8 weeks
Change in The 39-item Parkinson's Disease Questionnaire (PDQ-39) From Baseline to 8 Weeks.
The PDQ-39 contains 39-items covering 8 discrete dimensions: mobility, activities of daily living, emotional well-being, stigma, social support, cognitions, communication, and bodily discomfort. Each question is scored on a 5-point scale and recoded to 0 to 4 for the analysis. The total score can range from 0 to 132 and with a higher score indicating more severe symptoms.
Measured: baseline to 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2013 (estimated)
- Study startAug 2010
- Primary completionJun 2012
- Study completionJul 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Parkinson's Disease With DementiaStudies of the same condition, open and under way.
- More trials run by China Medical University HospitalThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- China Medical University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Science and Technology Council, Taiwan
- Responsible party
- Principal investigator, Chon-Haw Tsai, China Medical University Hospital
- Investigators
- Chon-Haw Tsai, MD, PHD, Principal investigator, Department of Neurology, China Medical University Hospital, Taichung, Taiwan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01785628
- Sponsor's protocol ID
- DMR98-IRB-296
- Status last verified
- Aug 2013
- First submitted
- 24 Jun 2011
- Last updated
- 22 Aug 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Tsai CH, Huang HC, Liu BL, Li CI, Lu MK, Chen X, Tsai MC, Yang YW, Lane HY. Activation of N-methyl-D-aspartate receptor glycine site temporally ameliorates neuropsychiatric symptoms of Parkinson's disease with dementia. Psychiatry Clin Neurosci. 2014 Sep;68(9):692-700. doi: 10.1111/pcn.12175. Epub 2014 Apr 14.
PubMed 24612097
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Impact of Pharmacological and Electric Modulation of NMDA Pathway on the Cognitive Flexibility and Volitional Movement Preparation in Patients With Parkinson's Disease
- ClinicalTrials.gov ID
- NCT01785628
- Acronym / sponsor ID
- DMR98-IRB-296
- Conditions
- Parkinson's Disease With Dementia
- Keywords
- Parkinson's disease, dementia, NMDA, event related potential, Bereitschaftspotential
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- China Medical University HospitalUniversity, hospital or other
- Collaborators
- National Science and Technology Council, Taiwan
- Study start
- Aug 2010
- Primary completion
- Jun 2012 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 7 Feb 2013 (estimated)
- Results
- Posted 22 Aug 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The project will investigate the effect of pharmacological and electric modulation of N-methyl-D-aspartate (NMDA) pathway on the cognitive flexibility and volitional movement preparation in patients with Parkinson's disease (PD).
Detailed description
Sarcosine (also called N-methylglycine) is an endogenous GlyT-1 inhibitor. By blocking glycine uptake, sarcosine increases synaptic glycine concentration to enhance NMDA receptor function. NMDA receptor, a subtype of ionotropic glutamate receptors, serves important functions in the brain, including learning, memory, cognition, and neural plasticity under physiological conditions and contributes to neurodegeneration in pathophysiological processes. NMDA receptor represents collectively a group of heteromeric tetramers. Every NMDA receptor is a protein complex, typically composed of two NR1 subunits and two NR2 subunits that together form the NMDA receptor ion channel. It requires two receptor agonists (glutamate for the NR2 binding site and glycine for the NR1 binding site) to open the ion channel for NMDA receptor activation. Clinically, modulation through the NMDA-NR1-glycine site is preferred to avoid the excitotoxicity associated with the glutamate site activation.8 In addition, recent animal studies have shown that dopamine secretion can be enhanced by either blocking the striatal NR2 or by activation of the NMDA-receptor glycine site. In the project, we will focus on pharmacological enhancement of NMDA-glycine receptor function based on increasing synaptic glycine concentration by sarcosine administration to examine whether enhancing NMDA-glycine receptor activity can improve the neuropsychiatric symptoms, cognition and hopefully motor function in PD-D patients
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sarcosine capsule | Experimental | Dietary Supplement: Sarcosine CapsuleOral capsules of Sarcosine (0.5g capsule) 1g / bid for 8 weeks. |
| Placebo capsule | Placebo comparator | Dietary Supplement: Placebo CapsuleOral capsules of Placebo (Dextrin 0.5g capsule) 1g / bid for 8 weeks. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- The diagnosis of PD-D will be based on the criteria proposed by 2007 movement disorders PD-D task force. (Emre M et.al. Mov Disord 2007; 22:1689-1707)
Key exclusion criteria (4 listed)
- Acute confusion due to systemic illnesses or drug intoxication.
- Major depression
- Features compatible with "Probable Vascular dementia.
- Patient who is pregnant.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sarcosine CapsuleSarcosine is a glycine transporter-1 (GlyT-1) inhibitor. By blocking glycine uptake, sarcosine increases synaptic glycine concentration to enhance NMDA receptor function. | Dietary supplement | Sarcosine capsule |
| Placebo CapsulePlacebo is dextrin composition. | Dietary supplement | Placebo capsule |
Primary outcome
Change in Unified Parkinson's Disease Rating Scale (UPDRS) From Baseline to 8 Weeks.
Time frame: baseline to 8 weeks.
Outcome is defined as change in total Unified Parkinson's Disease Rating Scale (UPDRS) between the baseline to 8 weeks. The UPDRS score has three parts, part I (Mentation, Behavior and Mood), Part II (Activities of Daily Living) and Part III (Motor Examination). Each consisting of questions answered on a 0-4 point scale. The minimum total score possible is 0 and the maximum total score possible is 176. Higher scores indicating more severe symptoms.
7 secondary outcomes
Change in Cognitive Abilities Screening Instrument (CASI) From Baseline to 8 Weeks.
Time frame: baseline to 8 weeks
Change in Clinical Dementia Rating (CDR) From Baseline to 8 Weeks.
Time frame: baseline to 8 weeks
Change in Neuropsychiatry Inventory (NPI) From Baseline to 8 Weeks.
Time frame: baseline to 8 weeks
Change in Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD) From Baseline to 8 Weeks.
Time frame: baseline to 8 weeks
Change in Hamilton Depression Rating Scale (HAM-D) From Baseline to 8 Weeks.
Time frame: baseline to 8 weeks
Change in Beck Depression Inventory-II (BDI-II) From Baseline to 8 Weeks.
Time frame: baseline to 8 weeks
Change in The 39-item Parkinson's Disease Questionnaire (PDQ-39) From Baseline to 8 Weeks.
Time frame: baseline to 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24612097Tsai CH, Huang HC, Liu BL, Li CI, Lu MK, Chen X, Tsai MC, Yang YW, Lane HY. Activation of N-methyl-D-aspartate receptor glycine site temporally ameliorates neuropsychiatric symptoms of Parkinson's disease with dementia. Psychiatry Clin Neurosci. 2014 Sep;68(9):692-700. doi: 10.1111/pcn.12175. Epub 2014 Apr 14.
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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.
Chon-Haw Tsai, MD, PHD principal investigator
Department of Neurology, China Medical University Hospital, Taichung, Taiwan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Sarcosine Capsule in people with Parkinson's Disease With Dementia, run by China Medical University Hospital at 1 site in Taiwan.
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 1 inclusion and 4 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 22 Aug 2013. 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 Taiwan. 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. Some participants in this study may receive a placebo. 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?
Yes. Results are posted in the registry (first posted 22 Aug 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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.
What does the primary outcome measure?
Change in Unified Parkinson's Disease Rating Scale (UPDRS) From Baseline to 8 Weeks. (time frame: baseline to 8 weeks.). 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 NCT01785628, which also lists 1 linked publication.
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 22 Aug 2013.