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Pioglitazone in Early Parkinson's Disease

2015年9月15日 更新者：University of Rochester

A Multi-Center, Double-Blind, Placebo-Controlled Phase II Study of Pioglitazone in Early Parkinson's Disease

This is a multi-center, double-blind, placebo controlled clinical trial of two dosages of oral pioglitazone (15 milligram(mg) and 45 milligram (mg)) for safety, tolerability, and futility.

Subjects who are on stable dose of rasagiline 1 mg/day or selegiline 10 mg/day for at least 8 weeks but no more than 8 months, will be randomized to one of two dosages of oral pioglitazone (15 mg and 45 mg) or matching placebo.

The study will measure disease progression by the change in total Unified Parkinson's Disease Rating Scale (UPDRS) score between the baseline visit and 44 weeks.

研究概览

地位

完全的

条件

干预/治疗

详细说明

A Multi-Center, Double-Blind, Placebo-Controlled Phase II Study of Pioglitazone in Early Parkinson's Disease (PD). The patient population has early stage PD (< 5 years from diagnosis), must be treated with 1 mg/day of rasagiline or 10 mg/day of selegiline for at least 8 weeks but not more than 8 months prior to enrollment.

The primary objective of this clinical trial is to assess the futility of pioglitazone on PD disease progression as measured by the change in total UPDRS score between the baseline visit and 44 weeks. The secondary objectives of the study are to collect additional efficacy and safety/tolerability data to be used in planning a subsequent Phase III trial of pioglitazone in early, treated PD. Measures of cognition, mood and blood- and urine-based biomarkers will also be explored. Subjects in this trial are randomly assigned in a 1:1:1 ratio to one of three study arms: 15 mg, 45 mg or placebo.

研究类型

介入性

注册 (实际的)

210

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 美国
    • Alabama
      • Birmingham、Alabama、美国、35294-0017
        • Univeristy of Alabama at Birmingham
    • Arizona
      • Phoenix、Arizona、美国、85013
        • Barrow Neurological Institute
    • California
      • Fountain Valley、California、美国、92708
        • The Parkinson's & Movement Disorder Institute
      • Los Angeles、California、美国、90083
        • University of Southern California
      • San Fransisco、California、美国、94143-0114
        • University of California San Fransisco
    • Colorado
      • Aurora、Colorado、美国、80045
        • Univeristy of Colorado Denver
    • Florida
      • Gainsville、Florida、美国、32610
        • University of Florida
      • Jacksonville、Florida、美国、32209
        • University of Florida, Jacksonville
      • Miami、Florida、美国、33136
        • University of Miami
      • Tampa、Florida、美国、33606
        • University of South Florida
    • Georgia
      • Atlanta、Georgia、美国、30329
        • Emory University School of Medicine
      • Augusta、Georgia、美国、30912
        • Medical College of Georgia
    • Hawaii
      • Honolulu、Hawaii、美国、96819
        • Pacific Health Research & Education Institute
    • Illinois
      • Chicago、Illinois、美国、60611
        • Northwestern University
      • Chicago、Illinois、美国、60612
        • Rush University Medical Center
    • Kansas
      • Kansas City、Kansas、美国、66160
        • University of Kansas Medical Center
    • Kentucky
      • Lexington、Kentucky、美国、40536
        • University of Kentucky
    • Louisiana
      • New Orleans、Louisiana、美国、70121
        • Ochsner Clinic Foundation
      • Shreveport、Louisiana、美国、71103
        • LSU Health Science Center Shreveport
    • Maryland
      • Baltimore、Maryland、美国、21287-0875
        • Johns Hopkins University
    • Massachusetts
      • Boston、Massachusetts、美国、02215
        • Beth Israel Deaconess Medical Center
      • Boston、Massachusetts、美国、02115
        • Brigham & Women's Hospital
    • Michigan
      • Ann Arbor、Michigan、美国、48109-5316
        • University of Michigan
      • East Lansing、Michigan、美国、48824
        • Michigan State University
    • Minnesota
      • Golden Valley、Minnesota、美国、55427
        • Struthers Parkinson's Center
    • Missouri
      • St Louis、Missouri、美国、63110
        • Washington University
    • New Hampshire
      • Lebanon、New Hampshire、美国、03756
        • Dartmouth Hitchcock Medical Center
    • New York
      • Brooklyn、New York、美国、11203-2098
        • SUNY Downstate Medical Center
      • Manhasset、New York、美国、11030
        • North Shore - LIJ Health System
    • North Carolina
      • Durham、North Carolina、美国、27705
        • Duke University
    • Oregon
      • Portland、Oregon、美国、97239-3098
        • Oregon Health & Science University
    • Pennsylvania
      • Philadelphia、Pennsylvania、美国、19107
        • Thomas Jefferson University
      • Philadelphia、Pennsylvania、美国、19107
        • University of Pennsylvania
    • South Carolina
      • Charleston、South Carolina、美国、29401
        • Medical University of South Carolina
    • Tennessee
      • Nashville、Tennessee、美国、37232
        • Vanderbilt University
    • Texas
      • Dallas、Texas、美国、75390-9036
        • University of Texas Southwestern Medical Center
    • Vermont
      • Burlington、Vermont、美国、05405
        • University of Vermont
    • Virginia
      • Charlottesville、Virginia、美国、22903
        • University of Virginia

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

30年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

  1. Willing and able to give informed consent.
  2. Men and women with idiopathic PD of less than 5 years duration from diagnosis with a Hoehn and Yahr Stage < 2.
  3. On stable dosage of rasagiline 1 mg/day or selegiline 10 mg/day for at least 8 weeks but not more than 8 months prior to baseline. Expected to remain on stable dose of rasagiline or selegiline as the only treatment for their PD for the duration of the study (44 weeks).
  4. Diagnosis must be confirmed by bradykinesia plus one of the other cardinal signs (resting tremor, rigidity) being present, without any other known or suspected cause of parkinsonism. The clinical signs must be asymmetric.
  5. Subjects may be taking stable doses (30 days) of anticholinergics or creatine (< 5gm/day) but must be expected to remain on the same dose.
  6. Age > 30 years.
  7. Women who are not postmenopausal or surgically sterile must use a medically accepted contraceptive regimen for at least 60 days before the baseline visit, and agree to continue such use throughout the duration of the study and for 30 days after the final dose of study drug.

Exclusion Criteria:

  1. Exposure to dopaminergic PD therapy or amantadine within 60 days prior to baseline visit or for 90 days or more at any point in the past
  2. Use of any of the following drugs within 180 days prior to baseline: neuroleptics, metoclopramide, alpha-methyldopa, clozapine, olanzapine and flunarizine.
  3. Use of any of the following drugs within 90 days prior to baseline: methylphenidate, cinnarizine, reserpine, tetrabenazine, amphetamine or monoamine oxidase (MAO)-A inhibitors (pargyline, phenelzine, and tranylcypromine).
  4. Presence of drug-induced parkinsonism (e.g., metoclopramide, flunarizine), metabolic identified neurogenetic disorders (e.g., Wilson's disease), encephalitis, or other atypical Parkinsonian syndromes (e.g., progressive supranuclear palsy, multiple system atrophy).
  5. Participation in other drug studies or receipt of other investigational drugs within 30 days prior to baseline or during the study.
  6. Presence of freezing.
  7. Any clinically significant psychiatric or medical condition or laboratory abnormality, which would in the judgment of the Investigator interfere with the subject's ability to participate.
  8. History of stereotaxic brain surgery for PD
  9. Clinically significant structural brain disease that the investigator believes would interfere with study evaluations.
  10. History of congestive heart failure.
  11. Use of pioglitazone or rosiglitazone within 90 days before randomization.
  12. Known intolerance to pioglitazone or rosiglitazone.
  13. Allergy to rasagiline or selegiline, or contraindication to rasagiline or selegiline use.
  14. Type I or Type II diabetes mellitus.
  15. HgbA1C greater than or equal to 6% at Screening.
  16. Known liver disease or elevation of AST or ALT greater than 2.5 times the upper limit of normal.
  17. Known history of osteoporosis. All women ≥ 65 years of age or men and woman at high risk of osteoporosis should have documented evidence of screening for osteoporosis. Factors associated with high risk of osteoporosis include: previous non traumatic fracture, chronic glucocorticoid use, body weight under 58 kg, family history of hip fracture, current cigarette smoking, and excessive alcohol intake.
  18. Drug or alcohol use or dependence that, in the opinion of the Investigator, would interfere with the safe conduct of the study.
  19. Significant peripheral edema (2+ or more) of the extremities of any etiology.
  20. Current or planned use of gemfibrozil or rifampin during the trial.
  21. History of bladder cancer.
  22. Evidence of hematuria which has not been evaluated for evidence of bladder cancer. (Documentation of work up or a repeat urine test that was negative for hematuria and the primary care physician or urologist does not feel that further work up is required.)
  23. History of macular edema.

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：四人间

武器和干预

参与者组/臂
干预/治疗
实验性的：15 mg pioglitazone
药品：Pioglitazone

Oral capsules of Pioglitazone (15 mg capsules) either 15 mg/qd or 45 mg/qd

Subjects will titrate in a blinded fashion to 30 mg/day after 2 weeks and to 45 mg per day) 2 weeks later as tolerated.

其他名称：
  • 盐酸吡格列酮
  • ACTOS (R)
实验性的：45 mg pioglitazone
药品：Pioglitazone

Oral capsules of Pioglitazone (15 mg capsules) either 15 mg/qd or 45 mg/qd

Subjects will titrate in a blinded fashion to 30 mg/day after 2 weeks and to 45 mg per day) 2 weeks later as tolerated.

其他名称：
  • 盐酸吡格列酮
  • ACTOS (R)
安慰剂比较：Matching Placebo
Placebo
药品：placebo
Placebo will contain microcrystalline cellulose. An over-encapsulation process will be conducted in accordance with Clinical Good Manufacturing Procedures (cGMP) regulations to create a dosage form for the active study drug that will be indistinguishable from the comparator (Placebo) capsule.

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Change in Total Unified Parkinson's Disease Rating Scale (UPDRS) Score From Baseline to 44 Weeks
大体时间：44 weeks

Change in total UPDRS score from baseline to 44 weeks (in subjects treated with rasagiline 1 mg/day or selegiline 10 mg/day).

The Total UPDRS is the sum of parts I, II, and III. The possible range of the total UPDRS is from 0-176. Higher values indicate worse outcomes.

The change is 44 weeks - baseline.
44 weeks

次要结果测量

结果测量
措施说明
大体时间
Change in Ambulatory Capacity From Baseline to 44 Weeks
大体时间：44 weeks

This is the sum of the 5 UPDRS questions regarding ambulatory capacity: falling, freezing, walking, gait, postural stability.

Ambulatory Capacity is calculated as the sum of items 13-15, 29, 30 of the Unified Parkinson's Disease Rating Scale (UPDRS). It ranges from 0-20. Higher scores are worse. Change is 44 weeks - baseline.
44 weeks
Change in Schwab and England Scale From Baseline to 44 Weeks
大体时间：44 weeks
The modified Schwab and England Activities of Daily Living is a single question ranging from 0-100% with anchors for each 10% interval. Higher scores are better (100% completely independent- 0% vegetative).
44 weeks
Change in Parkinson's Disease Questionnaire (PDQ-39) From Baseline to 44 Weeks
大体时间：44 weeks

The Parkinson's Disease Questionnaire (PDQ-39) is a short, 39 item measure of quality of life in subjects with Parkinson's disease. The questionnaire covers 8 aspects of quality of life: mobility, activities of daily living, emotional well-being, stigma, social support, cognitions, communication and bodily discomfort.

The total score ranges from 0 (never have difficulty) to 100 (always have difficulty). Lower scores reflect better quality of life.
44 weeks
Change in the Mattis Dementia Rating Scale (DRS-2)From Baseline to 44 Weeks
大体时间：44 weeks
The Mattis dementia rating scale is a psychometric instrument designed to assess the extent and nature of dementia. Mattis Dementia Rating scale (DRS-2) raw score is the sum of 5 raw sub-scores (attention has possible 37 points, initiation/perseveration has possible 37 points, construction has possible 6 points, conceptualization has possible 39 points, memory has possible 25 points). Total range is 0-144. Higher scores are better.
44 weeks
Change in the 15-item Geriatric Depression Scale (GDS-15)From Baseline to 44 Weeks
大体时间：44 weeks
The Geriatric Depression Scale - 15 is a short 15 yes or no question instrument for assessing depression in the elderly. It has been found to be particularly useful in assessing depression in Parkinson's Disease. A score of 0 to 5 is normal. A score greater than 5 suggests depression.
44 weeks

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

University of Rochester

合作者

National Institute of Neurological Disorders and Stroke (NINDS)
Michael J. Fox Foundation for Parkinson's Research

调查人员

  • 研究主任：Tanya Simuni, MD、Northwestern University
  • 研究主任：Karl Kieburtz, MD MPH、University of Rochester

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始

2011年3月1日

初级完成 (实际的)

2014年5月1日

研究完成 (实际的)

2014年5月1日

研究注册日期

首次提交

2010年12月3日

首先提交符合 QC 标准的

2011年1月18日

首次发布 (估计)

2011年1月20日

研究记录更新

最后更新发布 (估计)

2015年10月14日

上次提交的符合 QC 标准的更新

2015年9月15日

最后验证

2013年9月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • FS-ZONE
  • 5U01NS043128-12 (美国 NIH 拨款/合同)

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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