| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Abstract-- Background: Creatine and minocycline were prioritized for testing in Phase II clinical trials based on a systematic evaluation of potentially disease modifying compounds for Parkinson disease (PD). Objective: To test whether creatine and minocycline alter the course of early PD relative to a predetermined futility threshold for progression of PD in a randomized, double-blind, Phase II futility clinical trial. Agents that do not perform better than the futility threshold are rejected as futile and are not considered for further study. Methods: Participants had a diagnosis of PD within 5 years, but did not require medications for the management of symptoms. The primary outcome was the change in the total Unified Parkinson’s Disease Rating Scale (UPDRS) score from baseline to either the time when there was sufficient disability to warrant symptomatic therapy for PD or 12 months, whichever came first. Subjects were randomized 1:1:1 to receive creatine 10 g/day, minocycline 200 mg/day, or matching placebo. The futility threshold was set as a 30% reduction in UPDRS progression based on the placebo/tocopherol arm of the Deprenyl And Tocopherol Antioxidative Therapy Of Parkinsonism (DATATOP) trial. p Values 
0.1 indicate futility. Results: Two hundred subjects were randomized to the three groups. Neither creatine (p = 0.96) nor minocycline (p = 0.66) could be rejected as futile based on the DATATOP futility threshold. The rate of progression for the calibration placebo group fell outside the 95% CI for the DATATOP historical control. In a sensitivity analysis, based on the threshold derived from the calibration placebo group, again neither drug could be rejected as futile. Tolerability was 91% in the creatine group and 77% in the minocycline group. Common adverse events included upper respiratory symptoms (26%), joint pain (19%), and nausea (17%). Conclusions: Both creatine and minocycline should be considered for definitive Phase III trials to determine if they alter the long term progression of Parkinson disease (PD). Additional factors must be weighed before selecting agents for Phase III trials, including safety, tolerability, activity, cost, and availability of these two agents in comparison with other agents currently in development for PD.
This article has been cited by other articles:
|
|
 |
|
  H.-M. Gao, P. T. Kotzbauer, K. Uryu, S. Leight, J. Q. Trojanowski, and V. M.-Y. Lee Neuroinflammation and Oxidation/Nitration of {alpha}-Synuclein Linked to Dopaminergic Neurodegeneration J. Neurosci., July 23, 2008; 28(30): 7687 - 7698. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. P. Godoy, R. Tarelli, C. C. Ferrari, M. I. Sarchi, and F. J. Pitossi Central and systemic IL-1 exacerbates neurodegeneration and motor symptoms in a model of Parkinson's disease Brain, July 1, 2008; 131(7): 1880 - 1894. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Marras and A. Lang Invited Article: Changing concepts in Parkinson disease: Moving beyond the Decade of the Brain Neurology, May 20, 2008; 70(21): 1996 - 2003. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Bogdanov, W. R. Matson, L. Wang, T. Matson, R. Saunders-Pullman, S. S. Bressman, and M. F. Beal Metabolomic profiling to develop blood biomarkers for Parkinson's disease Brain, February 1, 2008; 131(2): 389 - 396. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Zhang, V. Anantharam, A. Kanthasamy, and A. G. Kanthasamy Neuroprotective Effect of Protein Kinase C{delta} Inhibitor Rottlerin in Cell Culture and Animal Models of Parkinson's Disease J. Pharmacol. Exp. Ther., September 1, 2007; 322(3): 913 - 922. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Ravina, R. Camicioli, P. G. Como, L. Marsh, J. Jankovic, D. Weintraub, and J. Elm The impact of depressive symptoms in early Parkinson disease Neurology, July 24, 2007; 69(4): 342 - 347. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Mitsumoto Mitochondrial Nutrition as a Strategy for Neuroprotection in Parkinson's Disease--Research Focus in the Department of Alternative Medicine and Experimental Therapeutics at Hokuriku University Evid. Based Complement. Altern. Med., June 1, 2007; 4(2): 263 - 265. [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Hass, M. A. Collins, and J. L. Juncos Resistance Training With Creatine Monohydrate Improves Upper-Body Strength in Patients With Parkinson Disease: A Randomized Trial Neurorehabil Neural Repair, March 1, 2007; 21(2): 107 - 115. [Abstract] [PDF]
|
|
|
|
 |
|
 B. C. Tilley and W. R. Galpern Screening Potential Therapies: Lessons Learned From New Paradigms Used in Parkinson Disease Stroke, February 1, 2007; 38(2): 800 - 803. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
The NINDS NET-PD Investigators A randomized clinical trial of coenzyme Q10 and GPI-1485 in early Parkinson disease Neurology, January 2, 2007; 68(1): 20 - 28. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. K. Cheung, P. H. Gordon, and B. Levin Selecting promising ALS therapies in clinical trials Neurology, November 28, 2006; 67(10): 1748 - 1751. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Bender, W. Koch, M. Elstner, Y. Schombacher, J. Bender, M. Moeschl, F. Gekeler, B. Muller-Myhsok, T. Gasser, K. Tatsch, et al. Creatine supplementation in Parkinson disease: A placebo-controlled randomized pilot trial. Neurology, October 10, 2006; 67(7): 1262 - 1264. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Schwid and G. R. Cutter Futility studies: Spending a little to save a lot Neurology, March 14, 2006; 66(5): 626 - 627. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
