Autologous Mesenchymal Stem Cell Therapy in Progressive Supranuclear Palsy: a Randomized, Double-blind, Controlled Clinical Trial

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



Sponsors


Source

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Oversight Info

Authority

Italy: Ministry of Health

Has Dmc

No


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

Overall Status

Recruiting

Start Date

2012-12-01

Completion Date

2014-12-01

Primary Completion Date

2014-12-01

Phase

Phase 1/Phase 2

Study Type

Interventional

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Treatment

Primary Outcome

Measure

Time Frame

Safety Issue

incidence of adverse events
one year
Yes

Secondary Outcome

Measure

Time Frame

Safety Issue

changes in brain images
one year
No

Enrollment

25

Condition


Intervention

Intervention Type

Biological

Intervention Name


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.

Arm Group Label

immediate stem cell therapy

delayed stem cell therapy



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

Gender

Both

Minimum Age

40 Years

Maximum Age

N/A

Healthy Volunteers

No


Overall Official

Last Name

Role

Affiliation

Rosaria Giordano, MD
Principal Investigator
IRCCS Ca' Granda Ospedale Maggiore Policlinico

Overall Contact

Last Name

Margherita Canesi, MD

Phone

0039 02 5799

Phone Ext

3353

Email

canesi@parkinson.it


Location

Facility

Status

Investigator

ICP Parkinson Institute
Milano 20126 Italy
Recruiting
Last Name: Gianni Pezzoli, MD
Role: Principal Investigator

Last Name: Margherita Canesi, MD
Role: Sub-Investigator


Location Countries

Country

Italy


Verification Date

2013-03-01

Lastchanged Date

2013-03-31

Firstreceived Date

2013-03-31

Responsible Party

Responsible Party Type

Sponsor


Keywords


Is Fda Regulated

No

Has Expanded Access

No

Condition Browse


Secondary Id

2011-004051-39

Number Of Arms

2

Arm Group

Arm Group Label

immediate stem cell therapy

Arm Group Type

Active Comparator

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 Group Label

delayed stem cell therapy

Arm Group Type

Sham Comparator

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



Firstreceived Results Date

N/A

Other Outcome

Measure

changes in motor function

Time Frame

one year

Safety Issue

No

Description

changes vs baseline in total and motor UPDRS scores, Hoehn & Yahr staging, SEADL score, CGI and multifactorial movement analysis


Measure

changes in cognitive functions

Time Frame

one year

Safety Issue

No

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)




Information obtained from ClinicalTrials.gov on April 04, 2013

Conditions

Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov, conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions

Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied. Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase

Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions that study is seeking to answer:

In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.



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