Cont. of a Study to Evaluate Implanting Peripheral Nerve Grafts Into Subjects With Parkinson's Disease (PD) During DBS

Parkinson's Disease Clinical Trial

— CAPNG  

Official title:

Continuation of a Pilot Study to Evaluate the Safety and Feasibility of Implanting Autologous Peripheral Nerve Grafts in Subjects With Parkinson's Disease Undergoing Deep Brain Stimulation Surgery and Treatment

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02369003
• Other study ID #: 14-0729-F6A
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: February 2015
• Est. completion date: September 2027

Study information

• Verified date: November 2023
• Source: University of Kentucky
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This pilot study is designed to follow up on a previous, preliminary study and test the long-term safety and feasibility of the implantation of autologous peripheral nerve grafts into the substantia nigra, basal forebrain, putamen, and/or STN of participants with PD undergoing deep brain stimulation (DBS) surgery. Peripheral nerve tissue contains Schwann cells which produce growth factors that have been demonstrated to support the survival and function of neurons.

Participants will serve as their own donor for the tissue, which will be implanted at the time they undergo DBS surgery.

Description:

The primary objective of this pilot study is to demonstrate safety of the approach:

introducing a minor modification of a standard, FDA approved neurosurgical procedure in use for over a decade to implant autologous peripheral nerve into the central nervous system. As such, the study is designed to pose minimal risk and minimal inconvenience to the subjects. Additionally, the test paradigm is performed strategically to not interfere with the surgery or delivery of the scheduled clinical DBS therapy. The scientific basis for this study is that the implanted peripheral nerve tissue is naturally well suited to provide multiple growth factors that have been shown experimentally to support the survival and function of dopaminergic neurons. Central to this proposal is the hypothesis that the implanted tissue will physiologically deliver growth factors to restore to normal function the afflicted neurons found in PD.

The first specific aim is to assess the feasibility and safety of the combined peripheral nerve graft/DBS surgical procedure. The second specific aim is to evaluate the long term clinical safety of the peripheral nerve implant.

This pilot study will provide safety data that can be used to generate a larger phase III clinical trial. If successful, it would herald the development of a new treatment for PD in which patients are able to provide their own tissue as a source of growth factors that could arrest or reverse the ongoing cellular loss that is responsible for their devastating dysfunction.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 70
• Est. completion date: September 2027
• Est. primary completion date: September 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

Inclusion Criteria:

• Undergoing DBS of the STN or GPi

• Between the ages of 40-75

• Able to give informed consent

• Show a positive response to Sinemet (carbidopa/levodopa)

• Be able to tolerate the surgical procedure

Exclusion Criteria:

• Any condition that would not make the subject a candidate for DBS of the STN or GPi

• Under the age of 40 or over the age of 75

• Unable to give informed consent

• Female who is pregnant, lactating, or of child-bearing potential unwilling to use an adequate birth control method during the period of the study

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

Procedure:
• Autologous Peripheral Nerve Graft
Implantation of Autologous Peripheral Nerve Graft into the substantia nigra, basal forebrain, putamen, and/or STN of participants with PD undergoing deep brain stimulation (DBS) surgery.

Locations

Country	Name	City	State
United States	University of Kentucky	Lexington	Kentucky

Sponsors (1)

Lead Sponsor	Collaborator
Craig van Horne, MD, PhD

Country where clinical trial is conducted

United States, 

References & Publications (10)

Chau MJ, Quintero JE, Monje PV, Voss SR, Welleford AS, Gerhardt GA, van Horne CG. Using a Transection Paradigm to Enhance the Repair Mechanisms of an Investigational Human Cell Therapy. Cell Transplant. 2022 Jan-Dec;31:9636897221123515. doi: 10.1177/09636897221123515. — View Citation

Colvett I, Gilmore A, Guzman S, Ledreux A, Quintero JE, Ginjupally DR, Gurwell JA, Slevin JT, Guduru Z, Gerhardt GA, van Horne CG, Granholm AC. Recipient Reaction and Composition of Autologous Sural Nerve Tissue Grafts into the Human Brain. J Clin Med. 20 — View Citation

El Seblani N, Welleford AS, Quintero JE, van Horne CG, Gerhardt GA. Invited review: Utilizing peripheral nerve regenerative elements to repair damage in the CNS. J Neurosci Methods. 2020 Apr 1;335:108623. doi: 10.1016/j.jneumeth.2020.108623. Epub 2020 Feb 3. — View Citation

Gera G, Guduru Z, Yamasaki T, Gurwell JA, Chau MJ, Krotinger A, Schmitt FA, Slevin JT, Gerhardt GA, van Horne C, Quintero JE. Gait and Balance Changes with Investigational Peripheral Nerve Cell Therapy during Deep Brain Stimulation in People with Parkinso — View Citation

Quintero JE, Slevin JT, Gurwell JA, McLouth CJ, El Khouli R, Chau MJ, Guduru Z, Gerhardt GA, van Horne CG. Direct delivery of an investigational cell therapy in patients with Parkinson's disease: an interim analysis of feasibility and safety of an open-la — View Citation

Slevin JT, Gerhardt GA, Smith CD, Gash DM, Kryscio R, Young B. Improvement of bilateral motor functions in patients with Parkinson disease through the unilateral intraputaminal infusion of glial cell line-derived neurotrophic factor. J Neurosurg. 2005 Feb;102(2):216-22. doi: 10.3171/jns.2005.102.2.0216. — View Citation

van Horne CG, Quintero JE, Gurwell JA, Wagner RP, Slevin JT, Gerhardt GA. Implantation of autologous peripheral nerve grafts into the substantia nigra of subjects with idiopathic Parkinson's disease treated with bilateral STN DBS: a report of safety and feasibility. J Neurosurg. 2017 Apr;126(4):1140-1147. doi: 10.3171/2016.2.JNS151988. Epub 2016 May 6. — View Citation

van Horne CG, Quintero JE, Slevin JT, Anderson-Mooney A, Gurwell JA, Welleford AS, Lamm JR, Wagner RP, Gerhardt GA. Peripheral nerve grafts implanted into the substantia nigra in patients with Parkinson's disease during deep brain stimulation surgery: 1-year follow-up study of safety, feasibility, and clinical outcome. J Neurosurg. 2018 Dec 1;129(6):1550-1561. doi: 10.3171/2017.8.JNS163222. — View Citation

van Horne CG, Vaughan SW, Massari C, Bennett M, Asfahani WS, Quintero JE, Gerhardt GA. Streamlining deep brain stimulation surgery by reversing the staging order. J Neurosurg. 2015 May;122(5):1042-7. doi: 10.3171/2014.9.JNS14619. Epub 2015 Mar 6. — View Citation

Welleford AS, Quintero JE, Seblani NE, Blalock E, Gunewardena S, Shapiro SM, Riordan SM, Huettl P, Guduru Z, Stanford JA, van Horne CG, Gerhardt GA. RNA Sequencing of Human Peripheral Nerve in Response to Injury: Distinctive Analysis of the Nerve Repair P — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Adverse Events as a Measure of Safety and Tolerability	Safety and Tolerability of Nerve Graft Implantation. Adverse events will be collected in order to measure the safety and tolerability of the grafting procedure. Adverse events will be documented and compared to the known and reported adverse events of DBS of Subthalamic Nucleus (STN) or internal globus pallidus (GPi).	15 years
Secondary	DaTscan assessment	Dopamine neurodegeneration at 12 or 24 months will be assessed using DaTscan SPECT imaging and compared to scans obtained before DBS surgery.	12 or 24 months