Embryonic Dopamine Cell Implants for Parkinson's Disease: A Double-Blind Study - Full Text View

Sponsor:	University of Colorado, Denver
Information provided by:	University of Colorado, Denver
ClinicalTrials.gov Identifier:	NCT00038116

Purpose

The purpose of this trial is to determine if patients who received embryonic dopamine cell implant surgery showed significantly greater improvement in their Parkinson's disease than a control group undergoing the placebo treatment, and to determine if the cell implant surgery was more effective in younger or older patients.

Condition	Intervention	Phase
Parkinson Disease	Procedure: embryonic dopamine cell implant surgery Procedure: placebo	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment

Resource links provided by NLM:

Genetics Home Reference related topics: familial paroxysmal nonkinesigenic dyskinesia Parkinson disease Perry syndrome

MedlinePlus related topics: Parkinson's Disease

Drug Information available for: Dopamine Dopamine hydrochloride

U.S. FDA Resources

Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:

a subjective Global Rating Scale [ Time Frame: duration of the trial ]

Secondary Outcome Measures:

objective measurements of PD, including UPDRS motor "off", Schwab and England "off", and 19F-fluorodopa uptake [ Time Frame: duration of the trial ]

Enrollment:	40
Study Start Date:	May 1995
Estimated Study Completion Date:	May 2008

Arms	Assigned Interventions
Active Comparator: 1	Procedure: embryonic dopamine cell implant surgery Half of the participants received the cell implant surgery, while the other half received the placebo. After the double-blind phase of the study, patients in the placebo group had the option of receiving tissue implants. Fourteen of these patients eventually had transplants.
Placebo Comparator: 2	Procedure: placebo sham surgery

Detailed Description:

Parkinson's disease is caused by the death of a small number of nerve cells that produce a critical chemical called dopamine. The drug L-dopa can partially make up for the lack of dopamine. As time goes on, however, most patients notice that the drugs do not work as well. Oftentimes, patients develop great fluctuations in motor control. Off drugs they cannot move, and on drugs they have excess, exaggerated movements. Research in animals over the last 20 years has shown that dopamine cells can be replaced by transplants of new cells obtained from fetal brain tissue. For the past 14 years, several laboratories around the world have been performing similar transplants of human fetal brain tissue on patients with Parkinson's disease. So far, it has been impossible to compare results from the different groups because no two centers are performing transplants in the same way.

This study seeks to get around that problem using a controlled clinical trial that compares the embryonic dopamine cell implant surgery with a placebo treatment. A total of 40 patients were recruited--half received the cell implant surgery, while the other half received the placebo. After the double-blind phase of the study, patients in the placebo group had the option of receiving tissue implants. Fourteen of these patients eventually had transplants. At present, this study is providing long-term follow-up evaluation and treatment for the subjects.

Eligibility

Ages Eligible for Study:	20 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

INCLUSION CRITERIA:

Idiopathic Parkinson's disease of at least 7 years duration and responsive to levodopa. Other Parkinson syndromes excluded.
Patients previously tried on other available forms of medical treatment.
Age between 20 and 75 years.
Presence of an intractable problem, such as "off" periods, dyskinesias, or "freezing," not controlled by dopamine agonists such as levodopa or pergolide.
No serious depression and no cognitive impairment.
Successful completion of home diary by patient or responsible party.
Successful videotape recordings at home of "on" and "off" status.
Normal MRI of brain within the last 18 months.
Fluorodopa PET scan compatible with idiopathic Parkinson's disease.
Medically fit to undergo implant surgery with certification by the patient's physician.
Able to financially cover expenses not paid for by NIH grant (between $1,000 and $2,000 for unreimbursed travel, video camera, and blood screening as specified in the consent form.

EXCLUSION CRITERIA:

Severe or moderately severe depression or cognitive impairment.
Previous brain surgery.
Presence of diabetes mellitus, severe cardiopulmonary disease or other severe medical disease, or MRI evidence of cerebrovascular disease.
Not medically cleared to undergo a surgical procedure.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00038116

Locations

United States, Colorado
University Hospital, the University of Colorado Health Sciences Center
Denver, Colorado, United States, 80262
United States, New York
North Shore University Hospital
Manhasset, New York, United States, 11030
The Movement Disorder Center, Columbia-Presbyterian Hospital
New York, New York, United States, 10032

Sponsors and Collaborators

University of Colorado, Denver

Investigators

Principal Investigator:

Curt R. Freed, M.D.

University of Colorado, Denver

More Information

Publications:

Ma Y, Tang C, Chaly T, Greene P, Breeze R, Fahn S, Freed C, Dhawan V, Eidelberg D. Dopamine cell implantation in Parkinson's disease: long-term clinical and (18)F-FDOPA PET outcomes. J Nucl Med. 2010 Jan;51(1):7-15. Epub 2009 Dec 15.

Freed, C.R., Greene, P.E., Breeze, R.E. Tsai, W.-Y., DuMouchel, W., Kao, R., Dillon, S., Winfield, H., Culver, S., Trojanowski, J.Q., Eidelberg, D., and Fahn, S.: Embryonic dopamine cell transplantation for severe Parkinson's disease. New England Journal of Medicine 344(10):710-719, 2001.

Nakamura T, Dhawan V, Chaly T, Fukuda M, Ma Y, Breeze R, Greene P, Fahn S, Freed C, Eidelberg D. Blinded positron emission tomography study of dopamine cell implantation for Parkinson's disease. Ann Neurol. 2001 Aug;50(2):181-7.

Ma Y, Feigin A, Dhawan V, Fukuda M, Shi Q, Greene P, Breeze R, Fahn S, Freed C, Eidelberg D. Dyskinesia after fetal cell transplantation for parkinsonism: a PET study. Ann Neurol. 2002 Nov;52(5):628-34.

Trott CT, Fahn S, Greene P, Dillon S, Winfield H, Winfield L, Kao R, Eidelberg D, Freed CR, Breeze RE, Stern Y. Cognition following bilateral implants of embryonic dopamine neurons in PD: a double blind study. Neurology. 2003 Jun 24;60(12):1938-43.

Bjorklund A., Dunnett S.B., Brundin P., Stoessl A.J., Freed C.R., Breeze R.E., Levivier M., Peschanski M., Studder L., Barker R. Neural transplantation for the treatment of Parkinson's disease. Lancet Neurology 2(7):437-45, 2003.

Freed CR, Leehey MA, Zawada M, Bjugstad K, Thompson L, Breeze RE. Do patients with Parkinson's disease benefit from embryonic dopamine cell transplantation? J Neurol. 2003 Oct;250 Suppl 3:III44-6.

Gordon PH, Yu Q, Qualls C, Winfield H, Dillon S, Greene PE, Fahn S, Breeze RE, Freed CR, Pullman SL. Reaction time and movement time after embryonic cell implantation in Parkinson disease. Arch Neurol. 2004 Jun;61(6):858-61.

McRae C, Cherin E, Yamazaki TG, Diem G, Vo AH, Russell D, Ellgring JH, Fahn S, Greene P, Dillon S, Winfield H, Bjugstad KB, Freed CR. Effects of perceived treatment on quality of life and medical outcomes in a double-blind placebo surgery trial. Arch Gen Psychiatry. 2004 Apr;61(4):412-20. Erratum in: Arch Gen Psychiatry. 2004 Jun;61(6):627.

ClinicalTrials.gov Identifier:	NCT00038116 History of Changes
Other Study ID Numbers:	R01NS32368
Study First Received:	May 29, 2002
Last Updated:	March 17, 2010
Health Authority:	United States: Federal Government

Keywords provided by University of Colorado, Denver:

Parkinson's disease
PD
dopamine
embryonic dopamine cell implant surgery
tissue implants

Additional relevant MeSH terms:

Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Dopamine
Dopamine Agents
Cardiotonic Agents

Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Protective Agents

ClinicalTrials.gov processed this record on February 12, 2012