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Clinical Trial to Evaluate Bone Marrow Stem Cell Therapy for PSP, a Rare Form of Parkinsonism

Primary Purpose

Progressive Supranuclear Palsy

Status
Unknown status
Phase
Phase 1
Locations
Italy
Study Type
Interventional
Intervention
stem cell therapy
Sponsored by
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Progressive Supranuclear Palsy focused on measuring Progressive Supranuclear palsy, stem cell therapy

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

diagnosis of 'probable Progressive Supranuclear Palsy - Richardson's disease subtype' according to current diagnostic criteria (Litvan et al. 1996 and 2003)

  • age at onset at least 40 years;
  • disease duration 12 months to 8 years;
  • supranuclear ophthalmoplegia;
  • postural instability or falls within 3 years from disease onset
  • positive MRI for PSP criteria (Quattrone et al, 2008)
  • Stable pharmacological treatment for at least 90 days
  • Lack of response to chronic levodopa (at least 12-month treatment).
  • Able to stand in upright posture without assistance for at least 30 seconds
  • Written informed consent (including video taping)

Exclusion Criteria:

  • Idiopathic Parkinson's disease;
  • Cerebellar ataxia
  • Symptomatic autonomic dysfunction
  • Evidence of any other neurological disease that could explain signs;
  • History of repeated strokes with stepwise progression of parkinsonian features;
  • History of major stroke;
  • Any history of severe or repeated head injury;
  • A history of encephalitis;
  • A history of neuroleptic use for a prolonged period of time or within the past 6 months;
  • Street-drug related parkinsonism;
  • Significant other neurological disease on CT-scan/MRI;
  • Oculogyric crises;
  • Major signs of corticobasal degeneration;
  • Signs of Lewy body disease;
  • Other life-threatening disease likely to interfere with the main outcome measure;
  • Any clinically significant laboratory abnormality, with the exception of cholesterol, triglycerides and glucose;
  • Renal failure (serum creatinine more than 300 mM/l);
  • Transaminase elevation more than twice the upper limit of normal;
  • Any concomitant disorder associated with bone marrow function impairment
  • Any concomitant disorder that requires chronic treatment with immunosuppressors, anti-inflammatory agents, and/or growth factors
  • dementia (MMSE < 24 according to Folstein 1975 or defined according to DSM-IV TR criteria)
  • any other disorder that could interfere with the evaluation of treatment or that could make intra-arterial infusion inadvisable
  • any other features that, according to the investigator, could reduce adherence to protocol procedures or prevent rapid access in case of emergency;
  • women of child-bearing age
  • participation in another clinical trial with experimental treatment in the last 30 days
  • brain MRI evidence of severe vascular abnormalities, space-occupying lesions or normal pressure hydrocephalus

Sites / Locations

  • ICP Parkinson InstituteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Sham Comparator

Arm Label

immediate stem cell therapy

delayed stem cell therapy

Arm Description

patients will undergo active intervention i.e. they will be given stem cell therapy immediately. After 6 months they will undergo a sham procedure.

patients allocated to delayed stem cell therapy will undergo a sham procedure (incannulation of the femoral vein and infusion of saline solution). They will receive stem cell therapy after 6 months

Outcomes

Primary Outcome Measures

incidence of adverse events
incidence of adverse events collected by clinical monitoring and performing routine laboratory tests

Secondary Outcome Measures

changes in brain images
change vs baseline in the striatal density of dopamine transporters in SPECT brain images and in the normalized regional cerebral flow / glucose metabolism in the gray matter in PET brain images after one year

Full Information

First Posted
March 31, 2013
Last Updated
March 31, 2013
Sponsor
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
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1. Study Identification

Unique Protocol Identification Number
NCT01824121
Brief Title
Clinical Trial to Evaluate Bone Marrow Stem Cell Therapy for PSP, a Rare Form of Parkinsonism
Official Title
Autologous Mesenchymal Stem Cell Therapy in Progressive Supranuclear Palsy: a Randomized, Double-blind, Controlled Clinical Trial
Study Type
Interventional

2. Study Status

Record Verification Date
March 2013
Overall Recruitment Status
Unknown status
Study Start Date
December 2012 (undefined)
Primary Completion Date
December 2014 (Anticipated)
Study Completion Date
December 2014 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
There is evidence suggesting that stem cells harvested from the bone marrow and transplanted into the brain may be effective in slowing down the progression of parkinsonism. Mesenchymal stem cells are able to produce growth factors that provide support to diseased nervous cells. In this study mesenchymal stem cells will be harvested from the bone marrow, cultivated in a test tube so that they multiply and then infused into the arteries that supply blood to the brain in 20 patients suffering from a rare form of parkinsonism, Progressive Supranuclear Palsy. Each patient will undergo two infusions, one with the stem cells and one without, at an interval of 6 months. The sequence of the two infusions will be assigned randomly; patients and assessors will not know the sequence (double-blind). Patients will be followed-up for up to 1 year after the last infusion, with regular assessments to assess safety, efficacy on motor and cognitive functions, and effects on the brain by neuroimaging techniques. The study has a preliminary phase with 5 patients all given stem cell therapy alone, designed to assess safety

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Progressive Supranuclear Palsy
Keywords
Progressive Supranuclear palsy, stem cell therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
immediate stem cell therapy
Arm Type
Active Comparator
Arm Description
patients will undergo active intervention i.e. they will be given stem cell therapy immediately. After 6 months they will undergo a sham procedure.
Arm Title
delayed stem cell therapy
Arm Type
Sham Comparator
Arm Description
patients allocated to delayed stem cell therapy will undergo a sham procedure (incannulation of the femoral vein and infusion of saline solution). They will receive stem cell therapy after 6 months
Intervention Type
Biological
Intervention Name(s)
stem cell therapy
Intervention Description
Bone marrow will be collected from the iliac crest under local anesthesia. Mesenchymal Stem Cells (MSCs) will be isolated and cultivated in vitro. Patients will be catheterized and the MSCs will then be administered by intra-arterial route via the internal carotid artery and the vertebral artery that is largest in caliber, injecting small boluses manually through a microcatheter.
Primary Outcome Measure Information:
Title
incidence of adverse events
Description
incidence of adverse events collected by clinical monitoring and performing routine laboratory tests
Time Frame
one year
Secondary Outcome Measure Information:
Title
changes in brain images
Description
change vs baseline in the striatal density of dopamine transporters in SPECT brain images and in the normalized regional cerebral flow / glucose metabolism in the gray matter in PET brain images after one year
Time Frame
one year
Other Pre-specified Outcome Measures:
Title
changes in motor function
Description
changes vs baseline in total and motor UPDRS scores, Hoehn & Yahr staging, SEADL score, CGI and multifactorial movement analysis
Time Frame
one year
Title
changes in cognitive functions
Description
changes vs baseline in MMSE score and in a series of neuropsychological measures (verbal comprehension, perceptual organization, immediate memory, delayed memory, word list recognition, language attention / concentration, visuospatial ability, processing speed, executive function)
Time Frame
one year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: diagnosis of 'probable Progressive Supranuclear Palsy - Richardson's disease subtype' according to current diagnostic criteria (Litvan et al. 1996 and 2003) age at onset at least 40 years; disease duration 12 months to 8 years; supranuclear ophthalmoplegia; postural instability or falls within 3 years from disease onset positive MRI for PSP criteria (Quattrone et al, 2008) Stable pharmacological treatment for at least 90 days Lack of response to chronic levodopa (at least 12-month treatment). Able to stand in upright posture without assistance for at least 30 seconds Written informed consent (including video taping) Exclusion Criteria: Idiopathic Parkinson's disease; Cerebellar ataxia Symptomatic autonomic dysfunction Evidence of any other neurological disease that could explain signs; History of repeated strokes with stepwise progression of parkinsonian features; History of major stroke; Any history of severe or repeated head injury; A history of encephalitis; A history of neuroleptic use for a prolonged period of time or within the past 6 months; Street-drug related parkinsonism; Significant other neurological disease on CT-scan/MRI; Oculogyric crises; Major signs of corticobasal degeneration; Signs of Lewy body disease; Other life-threatening disease likely to interfere with the main outcome measure; Any clinically significant laboratory abnormality, with the exception of cholesterol, triglycerides and glucose; Renal failure (serum creatinine more than 300 mM/l); Transaminase elevation more than twice the upper limit of normal; Any concomitant disorder associated with bone marrow function impairment Any concomitant disorder that requires chronic treatment with immunosuppressors, anti-inflammatory agents, and/or growth factors dementia (MMSE < 24 according to Folstein 1975 or defined according to DSM-IV TR criteria) any other disorder that could interfere with the evaluation of treatment or that could make intra-arterial infusion inadvisable any other features that, according to the investigator, could reduce adherence to protocol procedures or prevent rapid access in case of emergency; women of child-bearing age participation in another clinical trial with experimental treatment in the last 30 days brain MRI evidence of severe vascular abnormalities, space-occupying lesions or normal pressure hydrocephalus
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Margherita Canesi, MD
Phone
0039 02 5799
Ext
3353
Email
canesi@parkinson.it
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rosaria Giordano, MD
Organizational Affiliation
IRCCS Ca' Granda Ospedale Maggiore Policlinico
Official's Role
Principal Investigator
Facility Information:
Facility Name
ICP Parkinson Institute
City
Milano
ZIP/Postal Code
20126
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gianni Pezzoli, MD
First Name & Middle Initial & Last Name & Degree
Margherita Canesi, MD

12. IPD Sharing Statement

Citations:
PubMed Identifier
34712113
Citation
Giordano R, Canesi M, Isalberti M, Marfia G, Campanella R, Vincenti D, Cereda V, Ranghetti A, Palmisano C, Isaias IU, Benti R, Marotta G, Lazzari L, Montemurro T, Vigano M, Budelli S, Montelatici E, Lavazza C, Rivera-Ordaz A, Pezzoli G. Safety and Effectiveness of Cell Therapy in Neurodegenerative Diseases: Take-Home Messages From a Pilot Feasibility Phase I Study of Progressive Supranuclear Palsy. Front Neurosci. 2021 Oct 12;15:723227. doi: 10.3389/fnins.2021.723227. eCollection 2021.
Results Reference
derived
PubMed Identifier
27160012
Citation
Canesi M, Giordano R, Lazzari L, Isalberti M, Isaias IU, Benti R, Rampini P, Marotta G, Colombo A, Cereda E, Dipaola M, Montemurro T, Vigano M, Budelli S, Montelatici E, Lavazza C, Cortelezzi A, Pezzoli G. Finding a new therapeutic approach for no-option Parkinsonisms: mesenchymal stromal cells for progressive supranuclear palsy. J Transl Med. 2016 May 10;14(1):127. doi: 10.1186/s12967-016-0880-2.
Results Reference
derived
PubMed Identifier
24438512
Citation
Giordano R, Canesi M, Isalberti M, Isaias IU, Montemurro T, Vigano M, Montelatici E, Boldrin V, Benti R, Cortelezzi A, Fracchiolla N, Lazzari L, Pezzoli G. Autologous mesenchymal stem cell therapy for progressive supranuclear palsy: translation into a phase I controlled, randomized clinical study. J Transl Med. 2014 Jan 17;12:14. doi: 10.1186/1479-5876-12-14.
Results Reference
derived

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Clinical Trial to Evaluate Bone Marrow Stem Cell Therapy for PSP, a Rare Form of Parkinsonism

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