Parkinson's DiseaseTRANSEURONCT01898390
TRANSEURO Open Label Transplant Study in Parkinson's Disease
A study testing Transplant in people with Parkinson's Disease, run by University of Cambridge.
Trial summary
The Transeuro Transplant study is a trial which will involve grafting foetal tissue into the brain of patients with Parkinson's disease, who are already been followed in the observational study. The tissue inserted in the brain is to help replace and rebuild lost dopamine from the brain due to Parkinson's disease. Read more about this study
- Who is it for?
- Ages 30 to 68 years
- Conditions the study is for
- Parkinson's Disease
- What is being tested?
- Transplant
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- No sites listed yet
- Study dates
- May 2012to 31 Dec 2022
- Phase
- Interventional
- 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 30 to 68 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must meet ALL of the following criteria to be considered for the enrolment into this study:
- PD as defined using Queen's Square Brain Bank criteria.
- Disease duration ≥ 2 years and ≤ 13 years.
- Aged ≥ 30 years and ≤ 68 years at the time of grafting.
- Hoehn \& Yahr stage 2.5 or better when 'on'.
- On standard anti PD medication without significant LIDs defined as a score of >2 on the AIMS dyskinesia rating scale, in any body part.
- Patients must be right handed.
Who cannot join
- Any of the following will exclude patients from being enrolled in the study:
- Atypical or secondary parkinsonism including F-DOPA PET patterns consistent with this.
- Clinically significant response to Levodopa (as evaluated by the clinician) and/or apomorphine challenge.
- Mini-Mental State Examination (MMSE) score of less than 26.
- Unable to do normal copying of interlocking pentagons and semantic fluency score for naming animals of less than 20 over 90 seconds as these have recently been associated with the earlier onset of dementia in PD.
- Ongoing major medical or psychiatric disorder including depression and psychosis.
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- Other concomitant treatment with neuroleptics (inc. Atypical neuroleptics) and cholinesterase inhibitors.
- Significant drug induced dyskinesia defined as a score of >2 on the AIMS dyskinesia rating scale, in any body part.
- Previous neurosurgery, cell therapy or organ transplantation.
- Unable to be imaged using MRI.
- Any contraindication to immunosuppression therapy.
- Patients on anticoagulants
- Patients who are left handed
About this study
Official title: An Open Label Study to Assess the Safety and Efficacy of Neural Allo-Transplantation With Fetal Ventral Mesencephalic Tissue in Patients With Parkinson's Disease
The Transeuro Transplant study is a trial which will involve grafting foetal tissue into the brain of patients with Parkinson's disease, who are already been followed in the observational study. The tissue inserted in the brain is to help replace and rebuild lost dopamine from the brain due to Parkinson's disease.
Update April 2019:
A total of 11 PD patients were grafted in Cambridge, UK and Lund, Sweden. No further surgeries are planned. The final patient will complete the study's clinical endpoint (36 months post-graft) in 2021. We continue to assess these patients bi-annually alongside a control group which did not receive any intervention.
Read the detailed description
Clinical trials of cell therapy in PD patients were first performed in Lund in the late 1980s, followed by a number of similar, small trials in other European and North American centres. These initial studies performed on small groups of advanced PD patients were all open label but firmly established safety of the procedure. The results obtained in these trials have shown that the grafted dopaminergic [DA] neurons can survive and function long-term, over more than 10 years, and that some patients have shown clear clinical benefits, especially with respect to their bradykinesia and rigidity, with reductions in L-dopa requirements. Using functional imaging it has also been shown that the grafted DA neurons can restore striatal DA release and provide a sustained re-activation of motor cortical areas, i.e. key areas that were underactive prior to grafting.
Post-mortem studies have shown excellent long-term survival of the grafted DA neurons, notwithstanding the observation that some of the long-term surviving transplants (at 12-15 years after grafting) have now been shown to contain signs of PD-related pathologies, i.e. neuronal Lewy-bodies and alpha-synuclein positive inclusions in the grafts. However, such changes have been observed only in some and not in all patients and when seen the extent of the pathology is limited to a small number of the grafted DA cells and the clinical consequence, if any, not known.
However, the outcomes of two NIH sponsored double blind placebo controlled trials, which published their main findings in 2001 and 2003, have raised major concerns. In both these trials the grafted patients did not show any significant improvement overall compared to sham-operated controls at 1 and 2 years post grafting. Furthermore, a significant number of patients in both trials developed GIDs, which in some cases were so severe that further neurosurgery was needed to remedy the situation.
The reasons for the variable, and overall poor, outcome in these trials, including the generation of GIDs, have been the subject of much debate but have recently centred on three key elements, with an additional possible fourth element:
- The selection of patients in terms of clinical phenotype, disease stage and pattern of striatal dopaminergic denervation at the time of grafting;
- The differences in immunosuppressive regimes and the risk that incomplete immunosuppression in combination with the use of solid graft methods may lead to the development of detrimental immune/inflammatory reactions at the graft site with compromise of the grafted dopamine cell function;
- The mode of engraftment and differences in graft cell survival, and the risk for inhomogeneous delivery of dopaminergic neurons and the generation of potentially dyskinesia-inducing "patchy" innervations in the host striatum;
- A final possible element is the composition of the grafted tissue and the ratio of serotoninergic to dopaminergic neurons within the graft. There is emerging evidence that serotoninergic neurons can release dopamine in a relatively unregulated fashion given they lack transporters for it, and as such may use L-dopa as a false transmitter which may not only underlie the development of L-dopa induced dyskinesia's but may also contribute to GIDs.
Failure of the NIH trials to demonstrate any overall clinical benefits in the grafted patients, and the unexpected and worrisome development of GIDs in a significant number of patients in these trials has represented a major hurdle for the future development of cell based therapies for PD and it is in this and related areas that this project seeks to move the field forward and go beyond the current state of the art for this treatment approach.
This project has gathered together all the available expertise in this area to resolve or reduce the risk of the previous complications seen with VM transplants in patients with PD. We will conduct a new round of clinical trials, involving a step-by-step optimisation of all technical aspects of the grafting procedure and patient selection and assessment, in order to improve clinical efficiency and consistency, in the absence of troublesome dyskinesia's.
- Conditions
- Parkinson's Disease
- Being tested
- Transplant
- Keywords
- Parkinson's Disease, Allo-Transplantation, Fetal Ventral Mesencephalic Tissue
- Medical subject headings
- Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TransplantProcedure or surgery
Bilateral Neural Allo-Transplantation with Fetal Ventral Mesencephalic Tissue
| Study group | Role | What they receive |
|---|---|---|
| Transplant | Experimental | Neural Allo-Transplantation with Fetal Ventral Mesencephalic Tissue Receives: Procedure: Transplant |
| Control | No intervention | comparison group of controls, will receive the same observational and scanning assessments but will not receive any surgical procedures |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in UPDRS score
The change in motor Unified Parkinson's Disease Rating Scale (UPDRS)in a defined "OFF" state at 36 months post transplantation. "OFF" being defined as receiving no dopamine (DA) therapy for 12 hours prior to assessment or longer in the case of long acting dopamine agonists (e.g. Ropinirole slow release).
Measured: 36 months post transplantation
Secondary outcomes (7)
Change in timed motor tasks
Change in timed motor tasks at 36 months post transplantation
Measured: 36 months post transplantation
Number of dyskinesias at 36 months
The number of patients with dyskinesias (including L-dopa and graft induced dyskinesias) at 36 months post transplantation
Measured: 36 months post transplantation
L-dopa equivalent medication at 36 months
L-dopa equivalent medication doses at 36 months post transplantation.
Measured: 36 months post transplantation
L-dopa therapy at 36 months
Number of patients on L-dopa therapy at 36 months post transplantation.
Measured: 36 months post transplant
Off time medication at 36 months
The amount of 'off' time 36 months post transplantation
Measured: 36 months post transplantation
Quality of life change at 36 months
Quality of life (change) 36 months post transplantation
Measured: 36 months post transplantation
F-DOPA PET changes
Changes in F-DOPA PET in transplanted patients 36 months post transplantation
Measured: 36 months post transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2013 (estimated)
- Study startMay 2012
- Primary completion31 Dec 2022
- Study completion31 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Parkinson's DiseaseStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cambridge
- Sponsor type
- University, hospital or other
- Collaborators
- Lund University, Cardiff University, Imperial College London, University College, London, University Hospital Freiburg, Life Science Governance Institute, Assistance Publique - Hôpitaux de Paris, Institut National de la Santé Et de la Recherche Médicale, France, Life Technologies Ltd, part of Thermo Fisher Scientific, Inomed, Cambridge Cognition Ltd, Skane University Hospital, Imanova Limited
- Responsible party
- Principal investigator, Prof Roger Barker, University of Cambridge
- Investigators
- Roger Barker, Prof, Principal investigator, Department of Clinical Neurosciences, University of Cambridge
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01898390
- Sponsor's protocol ID
- TRANSEURO
- Other IDs
- FP7-242003
- Acronym
- TRANSEURO
- Status last verified
- May 2023
- First submitted
- 9 Jul 2013
- Last updated
- 25 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 25 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Study to Assess the Safety and Efficacy of Neural Allo-Transplantation With Fetal Ventral Mesencephalic Tissue in Patients With Parkinson's Disease
- ClinicalTrials.gov ID
- NCT01898390
- Acronym / sponsor ID
- TRANSEURO / TRANSEURO
- Conditions
- Parkinson's Disease
- Keywords
- Parkinson's Disease, Allo-Transplantation, Fetal Ventral Mesencephalic Tissue
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- University of CambridgeUniversity, hospital or other
- Collaborators
- Lund University, Cardiff University, Imperial College London, University College, London, University Hospital Freiburg, Life Science Governance Institute, Assistance Publique - Hôpitaux de Paris, Institut National de la Santé Et de la Recherche Médicale, France, Life Technologies Ltd, part of Thermo Fisher Scientific, Inomed, Cambridge Cognition Ltd, Skane University Hospital, Imanova Limited
- Study start
- May 2012
- Primary completion
- 31 Dec 2022 (actual)
- Study completion
- 31 Dec 2022 (actual)
- First posted
- 12 Jul 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.
The Transeuro Transplant study is a trial which will involve grafting foetal tissue into the brain of patients with Parkinson's disease, who are already been followed in the observational study. The tissue inserted in the brain is to help replace and rebuild lost dopamine from the brain due to Parkinson's disease.
Update April 2019:
A total of 11 PD patients were grafted in Cambridge, UK and Lund, Sweden. No further surgeries are planned. The final patient will complete the study's clinical endpoint (36 months post-graft) in 2021. We continue to assess these patients bi-annually alongside a control group which did not receive any intervention.
Detailed description
Clinical trials of cell therapy in PD patients were first performed in Lund in the late 1980s, followed by a number of similar, small trials in other European and North American centres. These initial studies performed on small groups of advanced PD patients were all open label but firmly established safety of the procedure. The results obtained in these trials have shown that the grafted dopaminergic [DA] neurons can survive and function long-term, over more than 10 years, and that some patients have shown clear clinical benefits, especially with respect to their bradykinesia and rigidity, with reductions in L-dopa requirements. Using functional imaging it has also been shown that the grafted DA neurons can restore striatal DA release and provide a sustained re-activation of motor cortical areas, i.e. key areas that were underactive prior to grafting.
Post-mortem studies have shown excellent long-term survival of the grafted DA neurons, notwithstanding the observation that some of the long-term surviving transplants (at 12-15 years after grafting) have now been shown to contain signs of PD-related pathologies, i.e. neuronal Lewy-bodies and alpha-synuclein positive inclusions in the grafts. However, such changes have been observed only in some and not in all patients and when seen the extent of the pathology is limited to a small number of the grafted DA cells and the clinical consequence, if any, not known.
However, the outcomes of two NIH sponsored double blind placebo controlled trials, which published their main findings in 2001 and 2003, have raised major concerns. In both these trials the grafted patients did not show any significant improvement overall compared to sham-operated controls at 1 and 2 years post grafting. Furthermore, a significant number of patients in both trials developed GIDs, which in some cases were so severe that further neurosurgery was needed to remedy the situation.
The reasons for the variable, and overall poor, outcome in these trials, including the generation of GIDs, have been the subject of much debate but have recently centred on three key elements, with an additional possible fourth element:
- The selection of patients in terms of clinical phenotype, disease stage and pattern of striatal dopaminergic denervation at the time of grafting;
- The differences in immunosuppressive regimes and the risk that incomplete immunosuppression in combination with the use of solid graft methods may lead to the development of detrimental immune/inflammatory reactions at the graft site with compromise of the grafted dopamine cell function;
- The mode of engraftment and differences in graft cell survival, and the risk for inhomogeneous delivery of dopaminergic neurons and the generation of potentially dyskinesia-inducing "patchy" innervations in the host striatum;
- A final possible element is the composition of the grafted tissue and the ratio of serotoninergic to dopaminergic neurons within the graft. There is emerging evidence that serotoninergic neurons can release dopamine in a relatively unregulated fashion given they lack transporters for it, and as such may use L-dopa as a false transmitter which may not only underlie the development of L-dopa induced dyskinesia's but may also contribute to GIDs.
Failure of the NIH trials to demonstrate any overall clinical benefits in the grafted patients, and the unexpected and worrisome development of GIDs in a significant number of patients in these trials has represented a major hurdle for the future development of cell based therapies for PD and it is in this and related areas that this project seeks to move the field forward and go beyond the current state of the art for this treatment approach.
This project has gathered together all the available expertise in this area to resolve or reduce the risk of the previous complications seen with VM transplants in patients with PD. We will conduct a new round of clinical trials, involving a step-by-step optimisation of all technical aspects of the grafting procedure and patient selection and assessment, in order to improve clinical efficiency and consistency, in the absence of troublesome dyskinesia's.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Transplant | Experimental | Procedure: TransplantNeural Allo-Transplantation with Fetal Ventral Mesencephalic Tissue |
| Control | No intervention | –comparison group of controls, will receive the same observational and scanning assessments but will not receive any surgical procedures |
Who may qualify
- Ages
- 30 to 68 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients must meet ALL of the following criteria to be considered for the enrolment into this study:
Key exclusion criteria (13 listed)
- Any of the following will exclude patients from being enrolled in the study:
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 |
|---|---|---|
| TransplantBilateral Neural Allo-Transplantation with Fetal Ventral Mesencephalic Tissue | Procedure or surgery | Transplant |
Primary outcome
Change in UPDRS score
Time frame: 36 months post transplantation
The change in motor Unified Parkinson's Disease Rating Scale (UPDRS)in a defined "OFF" state at 36 months post transplantation. "OFF" being defined as receiving no dopamine (DA) therapy for 12 hours prior to assessment or longer in the case of long acting dopamine agonists (e.g. Ropinirole slow release).
7 secondary outcomes
Change in timed motor tasks
Time frame: 36 months post transplantation
Number of dyskinesias at 36 months
Time frame: 36 months post transplantation
L-dopa equivalent medication at 36 months
Time frame: 36 months post transplantation
L-dopa therapy at 36 months
Time frame: 36 months post transplant
Off time medication at 36 months
Time frame: 36 months post transplantation
Quality of life change at 36 months
Time frame: 36 months post transplantation
F-DOPA PET changes
Time frame: 36 months post transplantation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 May 2023.
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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.
Roger Barker, Prof principal investigator
Department of Clinical Neurosciences, University of Cambridge
Questions about this trial
What is this clinical trial studying?
A study testing Transplant in people with Parkinson's Disease, run by University of Cambridge.
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 7 inclusion and 13 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: finished, as of the sponsor's last update on 25 May 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in UPDRS score (time frame: 36 months post transplantation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 25 May 2023.