Progressive Supranuclear PalsyPhase 1/2NCT01824121
Clinical Trial to Evaluate Bone Marrow Stem Cell Therapy for PSP, a Rare Form of Parkinsonism
A Phase 1/2 study testing stem cell therapy in people with Progressive Supranuclear Palsy, run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Progressive Supranuclear Palsy
- What is being tested?
- stem cell therapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 1 siteItaly
- Study dates
- Dec 2012to Dec 2014
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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)
Who cannot join
- 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;
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- 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
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
ICP Parkinson Institute
Milan, 20126
Gianni Pezzoli, MD
Margherita Canesi, MD
About this study
Official title: Autologous Mesenchymal Stem Cell Therapy in Progressive Supranuclear Palsy: a Randomized, Double-blind, Controlled Clinical Trial
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
- Conditions
- Progressive Supranuclear Palsy
- Being tested
- stem cell therapy
- Keywords
- Progressive Supranuclear palsy, stem cell therapy
- Medical subject headings
- Supranuclear Palsy, Progressive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
stem cell therapyBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| immediate stem cell therapy | Active comparator | patients will undergo active intervention i.e. they will be given stem cell therapy immediately. After 6 months they will undergo a sham procedure. Receives: Biological: stem cell therapy |
| delayed stem cell therapy | Sham comparator | 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 Receives: Biological: stem cell therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
incidence of adverse events
incidence of adverse events collected by clinical monitoring and performing routine laboratory tests
Measured: one year
Secondary outcomes (1)
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
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2013 (estimated)
- Study startDec 2012
- Primary completionDec 2014 (estimated)
- Study completionDec 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Progressive Supranuclear PalsyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Rosaria Giordano, MD, Principal investigator, IRCCS Ca' Granda Ospedale Maggiore Policlinico
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01824121
- Sponsor's protocol ID
- 032011
- Other IDs
- 2011-004051-39
- Status last verified
- Mar 2013
- First submitted
- 31 Mar 2013
- Last updated
- 4 Apr 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 34712113Canesi 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.
PubMed 27160012Giordano 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.
PubMed 24438512
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Autologous Mesenchymal Stem Cell Therapy in Progressive Supranuclear Palsy: a Randomized, Double-blind, Controlled Clinical Trial
- ClinicalTrials.gov ID
- NCT01824121
- Acronym / sponsor ID
- 032011
- Conditions
- Progressive Supranuclear Palsy
- Keywords
- Progressive Supranuclear palsy, stem cell therapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Fondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoUniversity, hospital or other
- Study start
- Dec 2012
- Primary completion
- Dec 2014 (estimated)
- Study completion
- Dec 2014 (estimated)
- First posted
- 4 Apr 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| immediate stem cell therapy | Active comparator | Biological: stem cell therapypatients will undergo active intervention i.e. they will be given stem cell therapy immediately. After 6 months they will undergo a sham procedure. |
| delayed stem cell therapy | Sham comparator | Biological: stem cell therapypatients 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 |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (26 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| stem cell therapyBone 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. | Biological | delayed stem cell therapy, immediate stem cell therapy |
Primary outcome
incidence of adverse events
Time frame: one year
incidence of adverse events collected by clinical monitoring and performing routine laboratory tests
1 secondary outcome
changes in brain images
Time frame: one year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2013.
- Derived from this study: PubMed 34712113Giordano 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.
- Derived from this study: PubMed 27160012Canesi 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.
- Derived from this study: PubMed 24438512Giordano 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rosaria Giordano, MD principal investigator
IRCCS Ca' Granda Ospedale Maggiore Policlinico
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing stem cell therapy in people with Progressive Supranuclear Palsy, run by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 4 Apr 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Margherita Canesi, MD (0039 02 5799 ext. 3353, canesi@parkinson.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
incidence of adverse events (time frame: one year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01824121, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Apr 2013.