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A Safety and Tolerability Study of Intracerebroventricular Administration of sNN0031 to Patients With Parkinson's Disease
This study is currently recruiting participants.
Verified by NeuroNova AB, March 2009
First Received: March 18, 2009   No Changes Posted
Sponsors and Collaborators: NeuroNova AB
Medtronic
Quintiles
Information provided by: NeuroNova AB
ClinicalTrials.gov Identifier: NCT00866502
  Purpose

This study is conducted to evaluate the safety and tolerability of the drug product sNN0031, containing Platelet Derived Growth Factor (PDGF), when administered directly into one of the fluid filled cavities in the brain using an implanted catheter and an implanted SynchroMed® II pump. Patients with a diagnosis of Parkinson's disease will be enrolled.


Condition Intervention Phase
Parkinson's Disease
Drug: Placebo
Phase I
Phase II

Genetics Home Reference related topics: familial paroxysmal nonkinesigenic dyskinesia Parkinson disease
MedlinePlus related topics: Parkinson's Disease
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety Study
Official Title: A Randomized, Double-Blind, Placebo Controlled, Safety and Tolerability Study of Intracerebroventricular Administration of sNN0031 to Patients With Idiopathic Parkinson's Disease (PD) of Moderate Severity, Using an Implanted Catheter and a SynchroMed® II Pump.

Further study details as provided by NeuroNova AB:

Primary Outcome Measures:
  • Safety and tolerability through assessment of adverse events, ECGs, vital signs, clinical laboratory variables, MRI of brain and spinal cord, CSF sampling, and device performance as characterized by catheter tip placement and infusion accuracy. [ Time Frame: Multiple over 3 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Time course of PD disease activity as measured by the UPDRS, MADRS and MMT rating scales. [ Time Frame: Multiple over 3 months ] [ Designated as safety issue: No ]
  • Change in caudate and putamen dopamine turnover using PET scans of 11C-PE2I uptake [ Time Frame: Baseline and at 3 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 12
Study Start Date: March 2009
Estimated Study Completion Date: March 2010
Estimated Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
sNN0031: Experimental
Continuous ICV infusion at one of three dose levels
Drug: Placebo
Continuous ICV infusion
Placebo: Placebo Comparator Drug: Placebo
Continuous ICV infusion

Detailed Description:

Tremor, rigidity, slow movement, poor balance, and difficulty walking are characteristic symptoms of Parkinson's disease (PD) that are associated with degeneration of dopamine-producing nerve cells in the brain. Administration of growth factors that stimulate neuronal stem and progenitor cells is one possible approach to restore the dopaminergic activity. The drug product sNN0031 containing the endogenous growth factor PDGF has been demonstrated to reduce the typical symptoms in animal models of PD.

NeuroNova intends to investigate whether intracerebroventricular administration of PDGF in the form of the drug product sNN0031 can improve motor function in patients with PD. In this first study the safety and tolerability of treatment for 2 weeks followed by 10 weeks follow-up will be evaluated.

  Eligibility

Ages Eligible for Study:   30 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female. Females should either be post-menopausal (at least 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with FSH levels >40 mIU/mL), be surgically sterilized (bilateral oophorectomy w/o hysterectomy), or use adequate contraception (oral contraceptives, intrauterine device or double barrier contraception, i.e., condom + diaphragm, condom or diaphragm + spermicidal gel or foam.) during the duration of the study.
  • Diagnosis of idiopathic Parkinson's disease (PD) of moderate severity (modified Hoehn & Yahr Stage IIb-III).
  • Effect duration of oral L-dopa dose intake ≤4 hours
  • Score ≥30 on motor part (part III) of UPDRS at defined off (>12 hours after last dose intake)
  • Dopaminergic responsiveness with at least 33% decrease in the UPDRS part III score after administration of L-dopa
  • Disease duration at least 5 years
  • Age 30 to 60 years
  • Stable anti-Parkinson treatment for at least 3 months
  • Ophthalmologic examination with normal findings regarding vascular structure and function
  • MRI examination of the brain and cervical spinal cord within 3 months before anticipated implantation of the device with no findings of tumors or potential sources of pathological bleedings, or abnormality that may interfere with the assessments of safety or efficacy or would, in the judgment of the investigator, represent a surgical risk to the subject.
  • Values of coagulation parameters including platelet count, normalized prothrombin complex (PK-INR), activated partial thromboplastin time (APTT) within normal ranges.
  • The subject is medically able to undergo the surgery required for stereotactic implantation of the catheter and infusion pump.
  • Has been given written and verbal information, has had opportunity to ask questions about the study, and understands time and procedural commitments
  • Signed consent (written) to participate in the study

Exclusion Criteria:

  • Atypical form of PD including repeated head trauma, drug- or toxin-induced PD, and other neurological conditions including Shy-Drager syndrome (multiple system atrophy), progressive supranuclear palsy, Wilson's disease, Huntington's disease, Hallervorden-Spatz syndrome, Alzheimer's disease, Creutzfeldt-Jakob disease, olivopontocerebellar atrophy, and post-traumatic encephalopathy
  • Concurrent dementia with a score of 20 or lower on the MMT rating scale
  • Concurrent clinically significant depression with a score of 16 or higher on the MADRS rating scale, equivalent to moderate or severe depression.
  • Exposure to neuroleptic drugs blocking dopamine receptors within 6 months
  • History of structural brain disease including tumors and hyperplasia
  • History of increased intracranial pressure
  • Prior surgical procedures or implantation of device for the treatment of PD
  • Prior exposure to any formulation of PDGF-BB (including topical)
  • Uncontrolled hypertension with blood pressure >160 mmHg systolic or >90 mmHg diastolic.
  • Any disorder that precludes a surgical procedure (eg, signs of sepsis or inadequately treated infection), alters wound healing (e.g. including bleeding disorders), or renders chronic ICV delivery or device implants medically unsuitable.
  • Presence of risk for increased or uncontrolled bleeding and/or risk of bleeding that is not managed optimally. Physicians should specifically investigate anatomical factors at or near the implant site (e.g., vascular abnormalities, neoplasms, or other abnormalities), underlying disorders of the coagulation cascade, platelet function, or platelet count (e.g., hemophilia, Von Willebrand's disease, liver disease, or other medical conditions), and the administration of any antiplatelet or anticoagulant medication (e.g., aspirin, Plavix, NSAIDs) in the pre- or perioperative period. Any of those conditions or drugs could place a patient at an increased risk for intraoperative or postoperative bleeding.
  • Presence of an implanted shunt for the drainage of cerebrospinal fluid (CSF) or an implanted central nervous system (CNS) catheter.
  • Presence of cardiac pacemakers, spinal cord stimulators, implantable programmable intraspinal drug pumps, or any other device that may interfere or interact with the programmer, without prior approval by Medtronic.
  • Clinically significant abnormalities in hematology or clinical chemistry parameters as assessed by the investigator
  • Ongoing medical condition that according to the investigator would interfere with the conduct and assessments in the study. Examples are medical disability (eg, severe degenerative arthritis, compromised nutritional state, peripheral neuropathy) that would interfere with the assessment of safety and efficacy of investigational product or device performance, or would compromise the ability of the subject to undergo study procedures (eg, MRI, PET), or to give informed consent.
  • Participation in another clinical trial with an investigational drug or device within 3 months prior to Screening visit.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00866502

Contacts
Contact: Sven Pålhagen, MD movementdisorder@karolinska.se

Locations
Sweden
Karolinska University Hospital, Huddinge Recruiting
Stockholm, Sweden, 141 86
Principal Investigator: Sven Pålhagen, MD            
Lund University Hospital Recruiting
Lund, Sweden, 22185
Principal Investigator: Håkan Widner, MD            
Sponsors and Collaborators
NeuroNova AB
Medtronic
Quintiles
Investigators
Principal Investigator: Sven Pålhagen, MD Karolinska University Hospital, Huddinge, Sweden
  More Information

No publications provided

Responsible Party: NeuroNova AB ( Markus Jerling, Chief Medical Officer )
Study ID Numbers: sNN0031-001, Q-26239
Study First Received: March 18, 2009
Last Updated: March 18, 2009
ClinicalTrials.gov Identifier: NCT00866502     History of Changes
Health Authority: Sweden: Medical Products Agency

Keywords provided by NeuroNova AB:
Parkinson
Safety
PDGF
Intracerebroventricular
Infusion
Device

Study placed in the following topic categories:
Ganglion Cysts
Movement Disorders
Parkinson Disease
Basal Ganglia Diseases
Central Nervous System Diseases
Parkinsonian Disorders
Neurodegenerative Diseases
Brain Diseases

Additional relevant MeSH terms:
Movement Disorders
Parkinson Disease
Nervous System Diseases
Basal Ganglia Diseases
Central Nervous System Diseases
Parkinsonian Disorders
Neurodegenerative Diseases
Brain Diseases

ClinicalTrials.gov processed this record on May 07, 2009