Pioglitazone in early Parkinson's disease: A phase 2, multicentre, double-blind, randomised trial

The Lancet Neurology

Volumn 14, Issue 8, 2015, Pages 795-803

  Simuni, Tanya ^a   Kieburtz, Karl ^b   Tilley, Barbara ^c   J Elm, Jordan ^d   Ravina, Bernard ^e   Babcock, Debra ^f   Emborg, Marina ^g   Hauser, Robert ^h   Kamp, Cornelia ^b   Morgan, John C ⁱ   Webster Ross, G ^j   K Simon, David ^k   Bainbridge, Jacci ^l   Baker, Liana ^b   Bodis Wollner, Ivan ^m   Boyd, James ⁿ   Cambi, Franca ^o   Carter, Julie ^p   Chou, Kelvin ^q   Dahodwala, Nabila ^r   Dewey, Richard B ^s   Dhall, Rohit ^t   Fang, John ^u   Farrow, Buff ⁱ   Feigin, Andrew ^v   Glazman, Sofya ^m   Goudreau, John ^w   LeBlanc, Pauline ^x   Lee, Stephen ^x   Leehey, Maureen ^l   Lew, Mark F ^y   Lowenhaupt, Stephanie ^z   Luo, Sheng ^c   Pahwa, Rajesh ^aa   Perez, Adriana ^c   Schneider, Jay ^ab   Scott, Burton ^ac   Shah, Binit ^c   Shannon, Kathleen M ^ad   Sharma, Saloni ^b   Singer, Carlos ^ae   Truong, Daniel ^af   Wagner, Renee ^o   Williams, Karen ^a   Marie Wills, Anne ^ag   Shieen Wong, Pei ^l,ah   Zadikoff, Cindy ^a   Zweig, Richard ^ai   more..

^a NORTHWESTERN UNIVERSITY   (United States)

^b UNIVERSITY OF ROCHESTER   (United States)

^c UNIVERSITY OF TEXAS   (United States)

^d MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

^e VOYAGER THERAPEUTICS   (United States)

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

^g UNIVERSITY OF WISCONSIN MADISON   (United States)

^h UNIVERSITY OF SOUTH FLORIDA   (United States)

ⁱ AUGUSTA UNIVERSITY   (United States)

^j Veterans' Affairs Pacific Island Health Care System   (United States)

^k HARVARD MEDICAL SCHOOL   (United States)

^l UNIVERSITY OF COLORADO   (United States)

^m SUNY DOWNSTATE MEDICAL CENTER   (United States)

ⁿ UNIVERSITY OF VERMONT   (United States)

^o UNIVERSITY OF KENTUCKY   (United States)

^p OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^q UNIVERSITY OF MICHIGAN   (United States)

^r UNIVERSITY OF PENNSYLVANIA   (United States)

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

^t BARROW NEUROLOGICAL INSTITUTE   (United States)

^u VANDERBILT UNIVERSITY   (United States)

^v FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH   (United States)

^w East Lansing   (United States)

^x DARTMOUTH HITCHCOCK MEDICAL CENTER   (United States)

^y UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^z UNIVERSITY OF VIRGINIA   (United States)

^aa UNIVERSITY OF KANSAS MEDICAL CENTER   (United States)

^ab THOMAS JEFFERSON UNIVERSITY   (United States)

^ac DUKE UNIVERSITY   (United States)

^ad RUSH UNIVERSITY MEDICAL CENTER   (United States)

^ae UNIVERSITY OF MIAMI   (United States)

^af Parkinson's and Movement Disorder Institute   (United States)

^ag BRIGHAM AND WOMEN S HOSPITAL   (United States)

^ah SINGAPORE GENERAL HOSPITAL   (Singapore)

^ai LOUISIANA STATE UNIVERSITY   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

CREATINE KINASE; PIOGLITAZONE; PLACEBO; RASAGILINE; SELEGILINE; 2,4 THIAZOLIDINEDIONE DERIVATIVE; INDAN DERIVATIVE; NEUROPROTECTIVE AGENT;

ADULT; ANKLE FRACTURE; ARTICLE; CARDIOVASCULAR DISEASE; CLINICAL DEMENTIA RATING; CONFUSION; CONTROLLED STUDY; CYST RUPTURE; DEHYDRATION; DEPRESSION; DIARRHEA; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG DOSE TITRATION; DRUG SAFETY; DRUG TOLERABILITY; DYSPNEA; EDEMA; FATIGUE; FEMALE; GERIATRIC DEPRESSION SCALE; HEART ATRIUM FLUTTER; HEART INFARCTION; HUMAN; HYPOXIA; INTENTION TO TREAT ANALYSIS; INTERVERTEBRAL DISK DEGENERATION; INTESTINE OBSTRUCTION; MAJOR CLINICAL STUDY; MALE; MIDDLE AGED; MULTICENTER STUDY; NAUSEA; NULL HYPOTHESIS; OSTEOARTHRITIS; PARKINSON DISEASE; PARKINSON DISEASE QUESTIONNAIRE 39; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; QUESTIONNAIRE; RANDOMIZED CONTROLLED TRIAL; RESPIRATORY FAILURE; SIDE EFFECT; SPONDYLOLISTHESIS; TRANSIENT ISCHEMIC ATTACK; TREATMENT OUTCOME; UNIFIED PARKINSON DISEASE RATING SCALE; UNITED STATES; AGED; CLINICAL TRIAL; DRUG COMBINATION;

AGED; DOUBLE-BLIND METHOD; DRUG THERAPY, COMBINATION; FEMALE; HUMANS; INDANS; MALE; MEDICAL FUTILITY; MIDDLE AGED; NEUROPROTECTIVE AGENTS; PARKINSON DISEASE; SELEGILINE; THIAZOLIDINEDIONES; TREATMENT OUTCOME;

EID: 84937520622     PISSN: 14744422     EISSN: 14744465     Source Type: Journal    
DOI: 10.1016/S1474-4422(15)00144-1     Document Type: Article

References (35)

1. de Lau LM, Breteler MM Epidemiology of Parkinson's disease. Lancet Neurol 2006, 5:525-535.
2. Suchowersky O, Gronseth G, Perlmutter J, Reich S, Zesiewicz T, Weiner WJ Practice parameter: neuroprotective strategies and alternative therapies for Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2006, 66:976-982.
3. Hart RG, Pearce LA, Ravina BM, Yaltho TC, Marler JR Neuroprotection trials in Parkinson's disease: systematic review. Mov Disord 2009, 24:647-654.
4. 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.
5. Chaturvedi RK, Beal MF PPAR: a therapeutic target in Parkinson's disease. J Neurochem 2008, 106:506-518.
6. Nicolakakis N, Aboulkassim T, Ongali B, et al. Complete rescue of cerebrovascular function in aged Alzheimer's disease transgenic mice by antioxidants and pioglitazone, a peroxisome proliferator-activated receptor gamma agonist. J Neurosci 2008, 28:9287-9296.
7. Risner ME, Saunders AM, Altman JF, et al. Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer's disease. Pharmacogenom J 2006, 6:246-254.
8. Ristow M Neurodegenerative disorders associated with diabetes mellitus. J Mol Med (Berl) 2004, 82:510-529.
9. Moreno S, Farioli-Vecchioli S, Ceru MP Immunolocalization of peroxisome proliferator-activated receptors and retinoid X receptors in the adult rat CNS. Neuroscience 2004, 123:131-145.
10. Storer PD, Xu J, Chavis J, Drew PD Peroxisome proliferator-activated receptor-gamma agonists inhibit the activation of microglia and astrocytes: implications for multiple sclerosis. J Neuroimmunol 2005, 161:113-122.
11. Eschbach J, von Einem B, Muller K, et al. Mutual exacerbation of peroxisome proliferator-activated receptor gamma coactivator 1alpha deregulation and alpha-synuclein oligomerization. Ann Neurol 2015, 77:15-32.
12. Swanson C, Emborg M Expression of peroxisome proliferator-activated receptor-gamma in the substantia nigra of hemiparkinsonian nonhuman primates. Neurol Res 2014, 36:634-646.
13. Swanson CR, Joers V, Bondarenko V, et al. The PPAR-gamma agonist pioglitazone modulates inflammation and induces neuroprotection in parkinsonian monkeys. J Neuroinflammation 2011, 8:91.
14. Dehmer T, Heneka MT, Sastre M, Dichgans J, Schulz JB Protection by pioglitazone in the MPTP model of Parkinson's disease correlates with I kappa B alpha induction and block of NF kappa B and iNOS activation. J Neurochem 2004, 88:494-501.
15. A randomized, double-blind, futility clinical trial of creatine and minocycline in early Parkinson disease. Neurology 2006, 66:664-671. NINDS NET-PD Investigators.
16. A randomized clinical trial of coenzyme Q10 and GPI-1485 in early Parkinson disease. Neurology 2007, 68:20-28. NINDS NET-PD Investigators.
17. Levin B The utility of futility. Stroke 2005, 36:2331-2332.
18. 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.
19. Fahn S, Elton R UPDRS Development Committee. The Unified Parkinson's Disease Rating Scale. Recent developments in Parkinson's disease 1987, 153-164. Macmillan Healthcare, Florham Park, NJ. S.M.C. Fahn, D.B. Calne, M. Goldstein (Eds.).
20. Hughes AJ, Daniel SE, Kilford L, Lees AJ Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 1992, 55:181-184.
21. Parashos SA, Elm J, Boyd JT, et al. Validation of an ambulatory capacity measure in Parkinson disease: a construct derived from the unified Parkinson's disease rating scale. J Parkinsons Dis 2015, 5:67-73.
22. Schwab RS, England AC Projection technique for evaluating surgery in Parkinson's disease. Third symposium on Parkinson's disease 1969, 152-157. E & S Livingstone, Edinburgh. F.J. Gillingham, I.M.L. Donaldson (Eds.).
23. Peto V, Jenkinson C, Fitzpatrick R, Greenhall R The development and validation of a short measure of functioning and well being for individuals with Parkinson's disease. Qual Life Res 1995, 4:241-248.
24. Pirogovsky E, Schiehser DM, Litvan I, et al. The utility of the Mattis Dementia Rating Scale in Parkinson's disease mild cognitive impairment. Parkinsonism Relat Disord 2014, 20:627-631.
25. Meara J, Mitchelmore E, Hobson P Use of the GDS-15 geriatric depression scale as a screening instrument for depressive symptomatology in patients with Parkinson's disease and their carers in the community. Age Ageing 1999, 28:35-38.
26. A controlled trial of rasagiline in early Parkinson disease: the TEMPO Study. Arch Neurol 2002, 59:1937-1943. Parkinson Study G.
27. Friedman LFC, DeMets D Fundamentals of clinical trials 1985, PSG Publishing Company, Littleton, MA. 2nd edn.
28. Rubin DB Multiple Imputation for nonresponse in surveys 1987, 166-167. John Wiley & Sons, New York.
29. Pagel-Langenickel I, Bao J, Joseph JJ, et al. PGC-1alpha integrates insulin signaling, mitochondrial regulation, and bioenergetic function in skeletal muscle. J Biol Chem 2008, 283(22):464-472.
30. Carta AR, Simuni T Thiazolidinediones under preclinical and early clinical development for the treatment of Parkinson's disease. Expert Opin Investig Drugs 2014, 24:1-9.
31. Parashos SA, Luo S, Biglan KM, et al. Measuring disease progression in early Parkinson disease: the National Institutes of Health Exploratory Trials in Parkinson Disease (NET-PD) experience. JAMA Neurol 2014, 71:710-716.
32. Lang AE, Melamed E, Poewe W, Rascol O Trial designs used to study neuroprotective therapy in Parkinson's disease. Mov Disord 2013, 28:86-95.
33. Beal MF, Oakes D, Shoulson I, et al. A randomized clinical trial of high-dosage coenzyme Q10 in early Parkinson disease: no evidence of benefit. JAMA Neurol 2014, 71:543-552. QE3 Investigators.
34. Parashos SA, Swearingen CJ, Biglan KM, et al. Determinants of the timing of symptomatic treatment in early Parkinson disease: the National Institutes of Health Exploratory Trials in Parkinson Disease (NET-PD) experience. Arch Neurol 2009, 66:1099-1104.
35. Kieburtz K, Tilley BC, Elm JJ, et al. Effect of creatine monohydrate on clinical progression in patients with Parkinson disease: a randomized clinical trial. JAMA 2015, 313:584-593. Writing Group for the NINDS Exploratory Trials in Parkinson Disease (NET-PD) Investigators.