A randomized, double-blind, futility clinical trial of creatine and minocycline in early Parkinson disease

Neurology

Volumn 66, Issue 5, 2006, Pages 664-671

  Ravina, Bernard ^a   Kieburtz, Karl ^b   Tilley, Barbara ^c   Shannon, Kathleen ^d,d   Tanner, Caroline ^e   Frederick Wooten, G ^f   Racette, Brad ^g   Deppen, Patricia ^g   Dewey, Richard B ^h   Hayward, Brigid ^h   Scott, Burton ⁱ   Field, Joanne ⁱ   Carter, Julie ^j   Brodsky, Matthew ^j   Andrews, Pamela ^j   Manyam, Bala ^k   Whetteckey, Jacqueline ^k   Rao, Jayaraman ^l   Cook, Maureen ^l   Aminoff, Michael J ^m   Christine, Chadwick ^m   Roth, Jessie ^m   Nance, Martha ⁿ   Parashos, Sotirios ⁿ   Peterson, Susan ⁿ   Jaglin, Jeana ^d   Singer, Carlos ^o   Perez, Marian A ^o   Blenke, Anita ^o   Hauser, Robert ^p   McClain, Theresa ^p   Wolfrath, Summer ^p   Dawson, Ted ^q   Dunlop, Becky ^q   Pahwa, Rajesh ^r   Lyons, Kelly ^r   Parsons, Amy ^r   Leehey, Maureen ^s   Bainbridge, Jacci ^s   Shulman, Lisa ^t   Weiner, William ^t   Pabst, Katharine ^t   Elble, Rodger ^u   Young, Charlene ^u   Sethi, Kapil ^v   Dill, Buff ^v   Martin, Wayne ^w   McInnes, Germaine ^w   Calabrese, Vincent P ^x   Roberge, Peggy ^x   Hamill, Robert ^y   Homan, Clare ^y   Bodis Wollner, Ivan G ^z   Hayes, Elizabeth ^z   Webster Ross, G ^aa   Terashita, Stephanie ^aa   Trugman, Joel ^f   Keller, Margaret F ^f   Sage, Jacob I ^ab   Caputo, Debbie ^ab   Fang, John ^ac   Shearon, Dorothy ^ac   Jennings, Danna ^ad   Kelsey, Tammie ^ad   Wojcieszek, Joanne ^ae   Feigin, Andrew ^af   Watts, Ray L ^ag   Stover, Natividad ^ag   McMurray, Rebecca ^ag   Albin, Roger ^ah   Wernette, Kristine ^ah   Siderowf, Andrew ^ai   Reichwein, Sue ^ai   Simon, David ^aj   Tarsy, Daniel ^aj   Scollins, Lisa ^aj   Tintner, Ron ^ak   Hunter, Christine ^ak   LeWitt, Peter ^al   Deangelis, Maryan ^al   Burns, Richard S ^am   Shill, Holly ^am   Danielson, Jill ^am   Marlor, Lynn ^am   Adler, Charles ^an   Lind, Marlene ^an   Gorell, Jay ^ao   Krstevska, Shana ^ao   Flewellen, Marilyn ^ao   Schneider, Jay ^ap   Sendek, Stephanie ^ap   Gollomp, Stephen ^ap   Vernon, Gwyn ^ap   Coffey, David ^aq   LeBlanc, Pauline ^aq   Lew, Mark F ^ar   Wu, Allan ^ar   Kawai, Connie ^ar   Uitti, Ryan ^as   Turk, Margaret ^as   Bower, James ^at   Torgrimson, Susan ^at   Handler, Joseph ^au   Greenbaum, Kathleen ^au   Sabbagh, Marwan ^av   Obradov, Zoran ^av   Elm, Jordan ^c   Guimaraes, Paulo ^c   Huang, Peng ^c   Palesch, Yuko ^c   Kamp, Cornelia ^b   Shinaman, Aileen ^b   Johnsen, Debbie ^b   Brocht, Alicia ^b   Bennett, Susan ^b   Weaver, Chris ^b   Goetz, Christopher ^d   Fagan, Susan ^aw   more..

^a NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE   (United States)

^b UNIVERSITY OF ROCHESTER   (United States)

^c MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

^d RUSH UNIVERSITY MEDICAL CENTER   (United States)

^e PARKINSON S INSTITUTE   (United States)

^f UNIVERSITY OF VIRGINIA   (United States)

^g WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^h UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

ⁱ DUKE UNIVERSITY   (United States)

^j OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^k SCOTT AND WHITE MEMORIAL HOSPITAL   (United States)

^l LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER   (United States)

^m UNIVERSITY OF CALIFORNIA   (United States)

ⁿ Struthers Parkinson's Center   (United States)

^o UNIVERSITY OF MIAMI   (United States)

^p UNIVERSITY OF SOUTH FLORIDA   (United States)

^q JOHNS HOPKINS UNIVERSITY   (United States)

^r UNIVERSITY OF KANSAS MEDICAL CENTER   (United States)

^s UNIVERSITY OF COLORADO   (United States)

^t UNIVERSITY OF MARYLAND   (United States)

^u SOUTHERN ILLINOIS UNIVERSITY   (United States)

^v MEDICAL COLLEGE OF GEORGIA   (United States)

^w UNIVERSITY OF ALBERTA   (Canada)

^x VETERANS AFFAIRS MEDICAL CENTER   (United States)

^y UNIVERSITY OF VERMONT   (United States)

^z SUNY DOWNSTATE MEDICAL CENTER   (United States)

^aa PACIFIC HEALTH RESEARCH INSTITUTE   (United States)

^ab ROBERT WOOD JOHNSON MEDICAL SCHOOL   (United States)

^ac VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

^ad INSTITUTE FOR NEURODEGENERATIVE DISORDERS   (United States)

^ae INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

^af NORTH SHORE UNIVERSITY HOSPITAL   (United States)

^ag UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^ah UNIVERSITY OF MICHIGAN   (United States)

^ai UNIVERSITY OF PENNSYLVANIA   (United States)

^aj BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

^ak BAYLOR COLLEGE OF MEDICINE   (United States)

^al WILLIAM BEAUMONT HOSPITAL   (United States)

^am BARROW NEUROLOGICAL INSTITUTE   (United States)

^an MAYO CLINIC   (United States)

^ao HENRY FORD HEALTH SYSTEM   (United States)

^ap THOMAS JEFFERSON UNIVERSITY   (United States)

^aq DARTMOUTH HITCHCOCK MEDICAL CENTER   (United States)

^ar UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^as MAYO CLINIC   (United States)

^at MAYO CLINIC ROCHESTER   (United States)

^au Neurology Associates   (United States)

^av SUN HEALTH RESEARCH INSTITUTE   (United States)

^aw UNIVERSITY OF GEORGIA   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

CREATINE; CREATININE; MINOCYCLINE; PLACEBO; SELEGILINE; TOCOPHEROL; UBIDECARENONE; ANTIINFECTIVE AGENT;

ADULT; AGED; ANEMIA; ARTHRALGIA; ARTICLE; BACKACHE; BALANCE DISORDER; CLINICAL TRIAL; CONSTIPATION; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CREATININE BLOOD LEVEL; DEPRESSION; DIARRHEA; DIZZINESS; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; DRUG TREATMENT FAILURE; EDEMA; FALLING; FATIGUE; FEMALE; FLU LIKE SYNDROME; FOLLOW UP; GASTROESOPHAGEAL REFLUX; HEADACHE; HEARTBURN; HUMAN; HYPERCHOLESTEROLEMIA; HYPERTENSION; KIDNEY DYSFUNCTION; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; NAUSEA; PARKINSON DISEASE; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RASH; RESPIRATORY TRACT DISEASE; SIDE EFFECT; SKIN DISCOLORATION; SLEEP DISORDER; TOOTH DISCOLORATION; TREATMENT OUTCOME; TREMOR; XEROSTOMIA; DISABLED PERSON; MIDDLE AGED; PATHOPHYSIOLOGY;

AGED; ANTI-BACTERIAL AGENTS; CREATINE; DISABLED PERSONS; DOUBLE-BLIND METHOD; FEMALE; HUMANS; MALE; MIDDLE AGED; MINOCYCLINE; PARKINSON DISEASE;

EID: 33645894705     PISSN: 00283878     EISSN: 1526632X     Source Type: Journal    
DOI: 10.1212/01.wnl.0000201252.57661.e1     Document Type: Article

References (42)

1. Ravina BM, Fagan SC, Hart RG, et al. Neuroprotective agents for clinical trials in Parkinson’s disease: a systematic assessment. Neurology 2003;60:1234-1240.
2. Persky AM, Brazeau GA. Clinical pharmacology of the dietary supplement creatine monohydrate. Pharmacol Rev 2001;53:161-176.
3. Sora I, Richman J, Santoro G, et al. The cloning and expression of a human creatine transporter. Biochem Biophys Res Commun 1994;204:419-427.
4. Tarnopolsky M, Parise G, Fu MH, et al. Acute and moderate-term creatine monohydrate supplementation does not affect creatine transporter mRNA or protein content in either young or elderly humans. Mol Cell Biochem 2003;244:159-166.
5. Jonas M, Cunha BA. Minocycline. Ther Drug Monit 1982;4:137-145.
6. Parker WD, Jr., Boyson SJ, Parks JK. Abnormalities of the electron transport chain in idiopathic Parkinson’s disease. Ann Neurol 1989;26:719-723.
7. Krige D, Carroll MT, Cooper JM, et al. Platelet mitochondrial function in Parkinson’s disease. The Royal Kings and Queens Parkinson Disease Research Group. Ann Neurol 1992;32:782-788.
8. Schapira AH, Cooper JM, Dexter D, et al. Mitochondrial complex I deficiency in Parkinson’s disease. J Neurochem 1990;54:823-827.
9. Matthews RT, Ferrante RJ, Klivenyi P, et al. Creatine and cyclocreatine attenuate MPTP neurotoxicity. Exp Neurol 1999;157:142-149.
10. Klivenyi P, Gardian G, Calingasan NY, et al. Additive neuroprotective effects of creatine and a cyclooxygenase 2 inhibitor against dopamine depletion in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease. J Mol Neurosci 2003;21:191-198.
11. Andreassen OA, Dedeoglu A, Ferrante RJ, et al. Creatine increase survival and delays motor symptoms in a transgenic animal model of Huntington’s disease. Neurobiol Dis 2001;8:479-491.
12. Ferrante RJ, Andreassen OA, Jenkins BG, et al. Neuroprotective effects of creatine in a transgenic mouse model of Huntington’s disease. J Neurosci 2000;20:4389-4397.
13. Klivenyi P, Ferrante RJ, Matthews RT, et al. Neuroprotective effects of creatine in a transgenic animal model of amyotrophic lateral sclerosis. Nat Med 1999;5:347-350.
14. Zhang W, Narayanan M, Friedlander RM. Additive neuroprotective effects of minocycline with creatine in a mouse model of ALS. Ann Neurol 2003;53:267-270.
15. Garner SE, Eady EA, Popescu C, et al. Minocycline for acne vulgaris:efficacy and safety. Cochrane Database Syst Rev 2003:CD002086.
16. Tilley BC, Alarcon GS, Heyse SP, et al. Minocycline in rheumatoid arthriti. A 48-week, double-blind, placebo-controlled trial. MIRA Trial Group Ann Intern Med 1995;122:81-89.
17. Hirsch EC, Breidert T, Rousselet E, et al. The role of glial reaction and inflammation in Parkinson’s disease. Ann NY Acad Sci 2003;991:214-228.
18. Du Y, Ma Z, Lin S, et al. Minocycline prevents nigrostriatal dopaminergic neurodegeneration in the MPTP model of Parkinson’s disease. Proc Natl Acad Sci USA 2001;98:14669-14674.
19. Wu DC, Jackson-Lewis V, Vila M, et al. Blockade of microglial activation is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson disease. J Neurosci 2002;22:1763-1771.
20. Chen M, Ona VO, Li M, et al. Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease. Nat Med 2000;6:797-801.
21. Kriz J, Nguyen MD, Julien JP. Minocycline slows disease progression in a mouse model of amyotrophic lateral sclerosis. Neurobiol Dis 2002; 10:268-278.
22. Smith DL, Woodman B, Mahal A, et al. Minocycline and doxycycline are not beneficial in a model of Huntington’s disease. Ann Neurol 2003; 54:186-196.
23. Yang L, Sugama S, Chirichigno JW, et al. Minocycline enhances MPTP toxicity to dopaminergic neurons. J Neurosci Res 2003;74:278-285.
24. Herson J. Predictive probability early termination plans for phase II clinical trials. Biometrics 1979;35:775-783.
25. Gehan EA. Update on planning of phase II clinical trials. Drugs Exp Clin Res 1986;12:43-50.
26. Elm JJ, Ravina B, Shannon K, et al. A responsive outcome for Parkinson’s disease neuroprotection futility studies. Ann Neurol 2005;57:197-203.
27. Tilley BC, Palesch YY, Kieburtz K, et al. Optimizing the ongoing search for new treatments for Parkinson disease: using futility designs. Neurology 2006;66:628-633.
28. Herson J, Carter SK. Calibrated phase II clinical trials in oncology. Stat Med 1986;5:441-447.
29. Effect of deprenyl on the progression of disability in early Parkinson’s disease. The Parkinson Study Group. N Engl J Med 1989;321:1364-1371.
30. Pocock SJ. The combination of randomized and historical controls in clinical trials. J Chronic Dis 1976;29:175-188.
31. Friedman L, Furberg C, DeMets D. Fundamentals of Clinical Trials. 2nd ed. Littleton, MA: John Wright-PSG Inc., 1985:94.
32. McKenna BE, Lamey PJ, Kennedy JG, Bateson J. Minocycline-induced staining of the adult permanent dentition: a review of the literature and report of a case. Dent Update 1999;26:160-162.
33. Cheek CC, Heymann HO. Dental and oral discolorations associated with minocycline and other tetracycline analogs. J Esthet Dent 1999; 11:43-48.
34. Shults CW, Oakes D, Kieburtz K, et al. Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline. Arch Neurol 2002;59:1541-1550.
35. Effect of lazabemide on the progression of disability in early Parkinson’s disease. The Parkinson Study Group. Ann Neurol 1996;40:99-107.
36. Fahn S, Oakes D, Shoulson I, et al. Levodopa and the progression of Parkinson’s disease. N Engl J Med 2004;351:2498-2508.
37. Green SBJ, Crowley J. Clinical trials in oncology. London: Chapman & Hall, 1997:44-47.
38. Kindt MV, Heikkila RE, Nicklas WJ. Mitochondrial and metabolic toxicity of 1-methyl-4-(2=-methylphenyl)-1,2,3,6-tetrahydropyridine. J Pharmacol Exp Ther 1987;242:858-863.
39. Haas RH, Nasirian F, Nakano K, et al. Low platelet mitochondrial complex I and complex II/III activity in early untreated Parkinson’s disease. Ann Neurol 1995;37:714-722.
40. Bonifati V, Rizzu P, van Baren MJ, et al. Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science 2003;299:256-259.
41. Canet-Aviles RM, Wilson MA, Miller DW, et al. The Parkinson’s disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization. Proc Natl Acad Sci USA 2004;101:9103-9108.
42. Valente EM, Abou-Sleiman PM, Caputo V, et al. Hereditary early-onset Parkinson’s disease caused by mutations in PINK1. Science 2004;304:1158-1160.