Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01141023




Registration number
NCT01141023
Ethics application status
Date submitted
8/06/2010
Date registered
10/06/2010
Date last updated
14/11/2023

Titles & IDs
Public title
Study to Identify Clinical, Imaging and Biologic Markers of Parkinson Disease Progression
Scientific title
The Parkinson's Progression Markers Initiative (PPMI)
Secondary ID [1] 0 0
PPMI-001
Universal Trial Number (UTN)
Trial acronym
PPMI
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Parkinson Disease 0 0
Condition category
Condition code
Neurological 0 0 0 0
Parkinson's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: Datscan SPECT Imaging - Subjects will b injected with 3-5 mCi of dopamine transporter. Within a 4 hour (+/- 30 minutes) window following the injection, subjects will undergo SPECT imaging on the camera.
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Mean Rates of Change
Timepoint [1] 0 0
Baseline to 156 months
Secondary outcome [1] 0 0
Comparison between Rates of Change
Timepoint [1] 0 0
Study intervals ranging from 3 months to 156 months
Secondary outcome [2] 0 0
Prevalence of measures of clinical, imaging and biomic outcomes in various subsets (
Timepoint [2] 0 0
study intervals ranging from baseline to 156 months.
Secondary outcome [3] 0 0
Predictive Value
Timepoint [3] 0 0
Baseline to 156 months
Secondary outcome [4] 0 0
To examine the proportion of SWEDD subjects that have a change in their clinical management at 24 months
Timepoint [4] 0 0
Baseline to 156 Months
Secondary outcome [5] 0 0
Exploratory Analysis
Timepoint [5] 0 0
Baseline to 156 months

Eligibility
Key inclusion criteria
Parkinson Disease (PD) Subjects:

* A diagnosis of Parkinson disease for 2 years or less at Screening.
* Confirmation from imaging core that screening DAT scan is consistent with dopamine transporter deficit, or if applicable a VMAT-2 PET scan consistent with vesicular monoamine transporter deficit.
* Not expected to require PD medication with at least 6 months from Baseline.
* Male or female age 30 years or older at time of PD diagnosis.

Healthy Control (HC) Subjects:

• Male or female age 30 years or older at Screening.
Minimum age
30 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Parkinson Disease (PD) Subjects:

* Currently taking levodopa, dopamine agonists, MAO-B inhibitors, amantadine or other PD medication.
* Has taken levodopa, dopamine agonists, MAO-B inhibitors or amantadine within 60 days of Baseline.
* Has taken levodopa or dopamine agonists prior to Baseline for more than a total of 60 days.
* Received any of the following drugs that might interfere with DAT imaging: Neuroleptics, metoclopramide, alpha methyldopa, methylphenidate, reserpine, or amphetamine derivative, within 6 months of Screening.
* Current treatment with anticoagulants (e.g., coumadin, heparin) that might preclude safe completion of the lumbar puncture.

If applicable, currently taking medications that are known to cause QT-prolongation, or are currently taking tetrabenazine (TBZ or amphetamine type medications.

* Condition that precludes the safe performance of routine lumbar puncture, such as prohibitive lumbar spinal disease, bleeding diathesis, or clinically significant coagulopathy or thrombocytopenia.
* Use of investigational drugs within 60 days prior to Baseline (dietary supplements taken outside of a clinical trial are not exclusionary, e.g., coenzyme Q10).

Healthy Control (HC) Subjects:

* Current or active neurological disorder.
* First degree relative with idiopathic PD (parent, sibling, child).
* MoCA score < 26.
* Received any of the following drugs that might interfere with DAT imaging: Neuroleptics, metoclopramide, alpha methyldopa, methylphenidate, reserpine, or amphetamine derivative, within 6 months of Screening.

If applicable, currently taking medications that are known to cause QT-prolongation, or are currently taking tetrabenazine (TBZ) or amphetamine type medications.

* Current treatment with anticoagulants (e.g., coumadin, heparin) that might preclude safe completion of the lumbar puncture.
* Condition that precludes the safe performance of routine lumbar puncture, such as prohibitive lumbar spinal disease, bleeding diathesis, or clinically significant coagulopathy or thrombocytopenia.
* Use of other investigational drugs within 60 days prior to baseline (dietary supplements taken outside of a clinical trial are not exclusionary, e.g., coenzyme Q10).

SWEDD Subjects:

All PD criteria apply, as above, except a SWEDD subject must have confirmation from imaging core that screening dopamine transporter SPECT scan shows no evidence of dopamine transporter deficit or if applicable a VMAT-2 PET scan shows no evidence of vesicular monoamine transporter deficit.

Prodromal Subjects:

Inclusion Criteria (Prodromal Subjects) 4.2.7.1. Subjects must have at least one of the following characteristics:

Hyposmia:

1. Male or female age 60 years or older
2. Confirmation from olfactory core that olfaction as determined by UPSIT is at or below the 10th percentile by age and gender

REM Behavior Disorder (RBD):

1. Male or female age 60 years or older
2. Confirmation from sleep core that subject's Polysomnography (PSG) meets criteria for RBD

LRRK2:

1. Male or female age 60 years or older
2. Written confirmation or documentation from testing facility that the individual is LRRK2 mutation positive 4.2.7.2. Confirmation from imaging core that screening dopamine transporter SPECT scan is read as eligible (see below). About 80 subjects will have a range of DAT deficit similar to subjects with early PD (mild to moderate DAT deficit). About 20 subjects will be selected with no DAT deficit or minimal DAT deficit similar in age, gender, and risk profile to those with mild to moderate DAT deficit. 4.2.7.3. Ability to provide written informed consent in accordance with Good Clinical Practice (GCP), International Conference on Harmonization (ICH), and local regulations. 4.2.7.4. Willing and able to comply with scheduled visits, required study procedures and laboratory tests. 4.2.7.5. Women may not be pregnant, lactating or planning pregnancy during the course of the study. Includes a negative urine pregnancy test on day of screening scan prior to injection (DaTSCAN).

Exclusion Criteria (Prodromal Subjects)

1. Current or active clinically significant neurological disorder or psychiatric disorder (in the opinion of the Investigator).
2. GDS score greater than or equal to 10 (GDS score of 5 - 9 requires Investigator discretion to enter study).
3. STAI Form Y-1 greater than or equal to 54 requires Investigator discretion to enter study.
4. A clinical diagnosis of dementia63 as determined by the investigator (Appendix 1).
5. A clinical diagnosis of Parkinson disease at the Screening visit as determined by the Investigator.
6. Received any of the following drugs that might interfere with dopamine transporter SPECT imaging: Neuroleptics, metoclopramide, alpha methyldopa, methylphenidate, reserpine, or amphetamine derivative, within 6 months of Screening.
7. Current treatment with anticoagulants (e.g., coumadin, heparin) that might preclude safe completion of the lumbar puncture.
8. Condition that precludes the safe performance of routine lumbar puncture, such as prohibitive lumbar spinal disease, bleeding diathesis, or clinically significant coagulopathy or thrombocytopenia.
9. Any other medical or psychiatric condition or lab abnormality, which in the opinion of the investigator might preclude participation.
10. Use of investigational drugs or devices within 60 days prior to Baseline (dietary supplements taken outside of a clinical trial are not exclusionary, e.g., coenzyme Q10).
11. Previously obtained MRI scan with evidence of clinically significant neurological disorder (in the opinion of the Investigator).

Genetic Cohort: Parkinson Disease Subjects - Inclusion:

1. Patients must have at least two of the following: resting tremor, bradykinesia, rigidity (must have either resting remor or bradykinesia) or either asymmetric resting tremor or asymmetric bradykinesia.
2. A diagnosis of Parkinson Disease for 7 years or less at screening.
3. Hoehn and Yahr state <4 at baseline
4. Male or female age 18 years or older
5. Willingness to undergo genetic testing and to be informed of genetic testing results.
6. Confirmation of mutation in LRRK2, GBA or SNCA
7. For subjects taking any drugs that might interfere with dopamine transporter SPECT imaging (Neuroleptics, metoclopramide, alpha methyldopa, methylphenidate, reserpine or amphetamine derivative must be willing and able from a medical standpoint to hold the medication for at least 5 half-lives prior to screening DatSCAN(TM) imaging.

Exclusion:

1. Current treatment with anticoagulants (e.g., coumadin, heparin) that might preclude safe completion of the lumbar puncture.
2. Condition that precludes the safe performance of routine lumbar puncture, such as prohibitive lumbar spinal disease, bleeding diathesis or clinically significant coagulopathy or thrombocytopenia.

Genetic cohort - Unaffected Individuals

Inclusion:

1. Male or female age 45 years or older at baseline with LRRK2 or GBA mutation and/or first degree relative with a LRRK2 or GBA mutation or
2. Male or female age 30 years or older at baseline with a SNCA mutation and/or a first degree relative with a SNCA mutation.
3. Unaffected subjects at high risk of LRRK2, GBA or SNCA mutation due to first degree relative with a LRRK2, GBA or SNCA mutation may choose either to be informed of the results or remain unaware of the results.
4. Unaffected subjects from an ethnic or geographic group knkown to have relatively high risk of LRRK2, GBA or SNCA mutation such as people of Ashkenazi Jewish or Basques descent) and who have a family member (either alive or deceased) who has/had PD must be willing to be informed of their own testing results.
5. Willingness to undergo genetic testing
6. For subjects taking any of the following drugs that might interfere with dopamine transporter SPECT imaging (neuroleptics, metoclopramide, alpha methyldopa, methylphenidate, reserpine or amphetamine derivative) must be willing and able from a medical standpoint to hold the medication for at least 5 half-lives prior to DatSCAN imaging.

Exclusion:

1. A clinical diagnosis of PD
2. Current treatment with anticoagulants (e.g. coumadin, heparin) that might preclude safe completion of the lumbar puncture.
3. Condition that precludes the safe performance of routine lumbar puncture, such as prohibitive lumbar spinal disease, bleeding diathesis or clinically significant coagulopathy or thrombocytopenia.

Genetic Registry - Inclusion:

1. Individual with a LRRK2, GBA or SNCA mutation and/or a first degree relative with a LRRK2, GBA or SNCA mutation.
2. Male or female age 18 years or older
3. Willingness to undergo genetic testing, but may choose either to be informed of the results or remain unaware of the results.

Study design
Purpose of the study
Other
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/06/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/06/2020
Sample size
Target
Accrual to date
Final
952
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Macquarie University - Sydney
Recruitment postcode(s) [1] 0 0
NSW2109 - Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
State/province [2] 0 0
Arizona
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United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
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Illinois
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United States of America
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Maryland
Country [9] 0 0
United States of America
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Massachusetts
Country [10] 0 0
United States of America
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New York
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
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Oregon
Country [13] 0 0
United States of America
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Pennsylvania
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
United States of America
State/province [15] 0 0
Washington
Country [16] 0 0
Austria
State/province [16] 0 0
Innsbruck
Country [17] 0 0
France
State/province [17] 0 0
Paris
Country [18] 0 0
Germany
State/province [18] 0 0
Kassel
Country [19] 0 0
Germany
State/province [19] 0 0
Tuebingen
Country [20] 0 0
Greece
State/province [20] 0 0
Athens
Country [21] 0 0
Israel
State/province [21] 0 0
Tel Aviv
Country [22] 0 0
Italy
State/province [22] 0 0
Napoli
Country [23] 0 0
Italy
State/province [23] 0 0
Salerno
Country [24] 0 0
Norway
State/province [24] 0 0
Trondheim
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Spain
State/province [25] 0 0
Barcelona
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Spain
State/province [26] 0 0
San Sebastian
Country [27] 0 0
United Kingdom
State/province [27] 0 0
London

Funding & Sponsors
Primary sponsor type
Other
Name
Ken Marek, MD
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Institute for Neurodegenerative Disorders
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Kenneth L Marek, MD
Address 0 0
Institute for Neurodegenerative Disorders
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT01141023