Double-blind Placebo Surgery Trial for Treatment of Parkinson's Disease

Transplantation of Embryonic Dopamine Neurons for Treatment of Parkinson's Disease: Double-blind Placebo Surgery Trial

A double-blind sham surgery-controlled trial was developed to determine the effectiveness of implantation of human embryonic dopamine neurons into the putamen of patients with advanced Parkinson's disease (PD), with half the patients receiving the implant (n = 20) and half receiving sham surgery (n = 20). The blind was maintained for 12 months before participants were told which surgery they received, at which time those receiving sham surgery could request the implant surgery.

A double-blind sham surgery-controlled trial was conducted to determine the effectiveness of implantation of human embryonic dopamine neurons into the putamen of patients with advanced Parkinson's disease (PD), with half the patients receiving the implant (n = 20) and half receiving sham surgery (n = 20). The goals were to determine whether the cells survived and led to improvement of symptoms, and to examine the effect of age on results of the implantation. Quality of life of participants and care partners was also examined at each of the assessment periods (baseline, 4, 8 and 12 months). The blind was maintained for 12 months.

In this double-blind study, 20 participants were randomly assigned to the treatment group and 20 to the sham surgery group with the blind being maintained for 12 months.

All of the above were "masked." Only the neurosurgeon (Dr. Breeze) who did the implant and the person in charge of random assignment were aware of which participant received which treatment.

Human embryonic dopamine neurons were implanted into brains of half the randomized participants (n = 20). Participants were evaluated at baseline, 4, 8, and 12 months after surgery.

This group (n = 20) received sham surgery with a steel frame affixed to their heads and four burr holes drilled into their foreheads without crossing the blood/brain barrier. Participants were assessed at baseline, 4, 8, and 12 months after surgery.

Cultured mesencephalic tissue from four embryos was implanted into the putamen bilaterally for those receiving the implant

one item scale where participants marked their answer on a scale ranging from -3 (much worse since surgery) to 0 (no change) to +3 (much improved since surgery)

Same scale was administered 7 days after surgery and prior to follow-up visits at Columbia at 4, 8, and 12 months after surgery and before the blind was lifted.

Inclusion Criteria: Diagnosed with Parkinson's disease (PD) for more than 7 years, improvement in response to levodopa, Positive Emission Tomography scan compatible with presence of PD, improvement of at least 33% on UPDRS after first morning dose of levodopa Exclusion Criteria: Mini-mental status exam score of less than 24, hallucinations during levodopa therapy, epilepsy, previous brain surgery, severe depression, another neurologic disorder, cardiovascular disease, and medical contraindication of surgery

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. Erratum In: Arch Gen Psychiatry. 2004 Jun;61(6):627.

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.

https://www.ncbi.nlm.nih.gov/pubmed?term=%22Archives+of+general+psychiatry%22%5BJour%5D+AND+2004%5Bpdat%5D+AND+McRae+C%5Bauthor%5D&cmd=detailssearch

https://www.ncbi.nlm.nih.gov/pubmed?term=%22The+New+England+journal+of+medicine%22%5BJour%5D+AND+344%5Bvolume%5D+AND+2001%5Bpdat%5D+AND+Freed%5Bfirst+author%5D+AND+Transplantation&TransSchema=title&cmd=detailssearch

Neurological and medical results of double-blind fetal transplant surgery as treatment for Parkinson's disease