Parkinson's Disease
Conditions
Keywords
Parkinson's disease, creatine, NET-PD, neuroprotection, PD
Brief summary
The purpose of this trial is to determine if the nutritional supplement creatine slows the progression of Parkinson's disease over time.
Detailed description
Parkinson's disease (PD) affects nearly a million Americans, a number that will increase over the coming decades as the population ages. Symptoms of PD may include tremor, rigidity or stiffness of the limbs and trunk, slowness of movement, and impaired balance and coordination. These problems occur because as PD worsens, some of the brain cells that control body movement die. This study will determine if creatine--an investigational compound--is able to slow the progression of PD. Creatine, a widely used dietary supplement is thought to improve exercise performance. In animal models and human studies, creatine has been shown to be well tolerated and may have some ability to protect brain cells. In the NET-PD LS-1 study, 1,720 participants will be randomly assigned to receive either creatine or a placebo (inactive substance). Participation in this study lasts a minimum of 5 years and includes at least 9 follow-up clinic visits and at least 3 telephone calls.
Interventions
DRUGcreatine
Creatine, a widely used dietary supplement is thought to improve exercise performance. In animal models and human studies, creatine has been shown to be well tolerated and may have some ability to protect brain cells. The study is comparing creatine 5 grams twice daily with placebo.
OTHERplacebo
an inactive substance
Sponsors
National Institute of Neurological Disorders and Stroke (NINDS)
University of Rochester
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Willing and able to give informed consent and willing to commit to long-term follow-up * PD (asymmetric features including slowness (bradykinesia) plus resting tremor and/or rigidity) within 5 years of diagnosis * Treated/responsive to dopaminergic therapy (dopamine agonists or levodopa) for at least 90 days, but not more than 2 years.
Exclusion criteria
* Use of creatine 14 days prior to baseline or during the study * History of known hypersensitivity or intolerability to creatine * Any unstable or clinically significant condition that would impair the subject's ability to comply with long term study follow-up * Other know or suspected causes of parkinsonism (e.g. metabolic, drug induced, etc.), or any significant features suggestive of a diagnosis of atypical parkinsonism.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Global Outcome Combined Information on Change From Baseline in Schwab England Activities of Daily Living, 39-Item Parkinson's Disease Questionnaire, Ambulatory Capacity, Symbol Digit Modalities, and Modified Rankin at 5 Years. | Change from baseline to 5 YEARS | All outcomes were coded such that higher scores indicated worse outcomes. Patients were ranked on each outcome and their ranks were summed (summed-ranks). Higher summed ranks (range, 5-4775) indicate worse outcomes. The mean summed ranks were compared by treatment group by a global statistical test (GST). |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo placebo: an inactive substance | 867 |
| Creatine creatine 5 grams twice daily | 874 |
| Total | 1,741 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 31 | 40 |
| Overall Study | Lost to Follow-up | 36 | 37 |
| Overall Study | Physician Decision | 13 | 12 |
| Overall Study | Protocol Violation | 8 | 7 |
| Overall Study | Study was stopped | 324 | 328 |
| Overall Study | Withdrawal by Subject | 110 | 110 |
Baseline characteristics
| Characteristic | Placebo | Creatine | Total |
|---|---|---|---|
| Age, Continuous | 61.5 years STANDARD_DEVIATION 9.6 | 62.1 years STANDARD_DEVIATION 9.7 | 61.8 years STANDARD_DEVIATION 9.6 |
| Sex: Female, Male Female | 313 Participants | 305 Participants | 618 Participants |
| Sex: Female, Male Male | 554 Participants | 569 Participants | 1123 Participants |
| Time since diagnosis, y | 1.6 years STANDARD_DEVIATION 1.1 | 1.5 years STANDARD_DEVIATION 1.1 | 1.5 years STANDARD_DEVIATION 1.1 |
| Total Unified Parkinson's Disease Rating Scale (UPDRS) | 25.9 units on a scale STANDARD_DEVIATION 11 | 26.5 units on a scale STANDARD_DEVIATION 11.7 | 26.2 units on a scale STANDARD_DEVIATION 11.4 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 687 / 867 | 698 / 874 |
| serious Total, serious adverse events | 347 / 867 | 315 / 874 |
Outcome results
Primary
The Global Outcome Combined Information on Change From Baseline in Schwab England Activities of Daily Living, 39-Item Parkinson's Disease Questionnaire, Ambulatory Capacity, Symbol Digit Modalities, and Modified Rankin at 5 Years.
All outcomes were coded such that higher scores indicated worse outcomes. Patients were ranked on each outcome and their ranks were summed (summed-ranks). Higher summed ranks (range, 5-4775) indicate worse outcomes. The mean summed ranks were compared by treatment group by a global statistical test (GST).
Time frame: Change from baseline to 5 YEARS
Population: Intent-to-Treat sample: n = 955, participants randomized at least 5 years before July 2013 (time of planned interim analysis).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | The Global Outcome Combined Information on Change From Baseline in Schwab England Activities of Daily Living, 39-Item Parkinson's Disease Questionnaire, Ambulatory Capacity, Symbol Digit Modalities, and Modified Rankin at 5 Years. | 2360 summed-ranks |
| Creatine | The Global Outcome Combined Information on Change From Baseline in Schwab England Activities of Daily Living, 39-Item Parkinson's Disease Questionnaire, Ambulatory Capacity, Symbol Digit Modalities, and Modified Rankin at 5 Years. | 2414 summed-ranks |
p-value: 0.45Global Statistical Test