Embryonic Dopamine Cell Implants for Parkinson's Disease

NCT ID: NCT00038116

Last Updated: 2013-02-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1995-05-31
• Study Completion Date: 2009-08-31

Brief Summary

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.

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.

Conditions

Parkinson Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

embryonic dopamine cell implant surgery

embryonic dopamine cell implant surgery

Group Type: ACTIVE_COMPARATOR

embryonic dopamine cell implant surgery

Intervention Type: PROCEDURE

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.

sham surgery

sham surgery (placebo)

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: PROCEDURE

sham surgery

Interventions

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.

Intervention Type: PROCEDURE

placebo

sham surgery

Intervention Type: PROCEDURE

Eligibility 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.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Curt R. Freed, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

University Hospital, the University of Colorado Health Sciences Center

Denver, Colorado, United States

North Shore University Hospital

Manhasset, New York, United States

The Movement Disorder Center, Columbia-Presbyterian Hospital

New York, New York, United States

Countries

United States

References

Freed CR, Greene PE, Breeze RE, Tsai WY, DuMouchel W, Kao R, Dillon S, Winfield H, Culver S, Trojanowski JQ, Eidelberg D, Fahn S. Transplantation of embryonic dopamine neurons for severe Parkinson's disease. N Engl J Med. 2001 Mar 8;344(10):710-9. doi: 10.1056/NEJM200103083441002.

Reference Type: BACKGROUND

PMID: 11236774 (View on PubMed)

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. doi: 10.1002/ana.1075.

Reference Type: BACKGROUND

PMID: 11506400 (View on PubMed)

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. doi: 10.1002/ana.10359.

Reference Type: BACKGROUND

PMID: 12402261 (View on PubMed)

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. doi: 10.1212/01.wnl.0000070181.28651.3b.

Reference Type: BACKGROUND

PMID: 12821736 (View on PubMed)

Bjorklund A, Dunnett SB, Brundin P, Stoessl AJ, Freed CR, Breeze RE, Levivier M, Peschanski M, Studer L, Barker R. Neural transplantation for the treatment of Parkinson's disease. Lancet Neurol. 2003 Jul;2(7):437-45. doi: 10.1016/s1474-4422(03)00442-3. No abstract available.

Reference Type: BACKGROUND

PMID: 12849125 (View on PubMed)

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. doi: 10.1007/s00415-003-1308-5.

Reference Type: BACKGROUND

PMID: 14579124 (View on PubMed)

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. doi: 10.1001/archneur.61.6.858.

Reference Type: BACKGROUND

PMID: 15210522 (View on PubMed)

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. doi: 10.1001/archpsyc.61.4.412.

Reference Type: BACKGROUND

PMID: 15066900 (View on PubMed)

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. doi: 10.2967/jnumed.109.066811. Epub 2009 Dec 15.

Reference Type: RESULT

PMID: 20008998 (View on PubMed)

Other Identifiers

93-0097

Identifier Type: -

Identifier Source: org_study_id