Cerebral PalsyPhase 1/2ACCeNT-CPNCT03473301
A Study of UCB and MSCs in Children With CP: ACCeNT-CP
A Phase 1/2 study testing Infusion of allogeneic umbilical cord blood and Infusion of MSCs in people with Cerebral Palsy, run by Joanne Kurtzberg, MD at 1 site in United States.
Trial summary
The main purpose of this study is to estimate change in motor function 12 months after treatment with a single dose of allogeneic umbilical cord blood (AlloCB) or repeated doses of umbilical cord tissue-derived mesenchymal stromal cells (hCT-MSC) in children with cerebral palsy. Read more about this study
- Who is it for?
- Ages 24 to 60 months
- Conditions the study is for
- Cerebral Palsy
- What is being tested?
- Infusion of allogeneic umbilical cord blood and Infusion of MSCs
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 91 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Apr 2018to 31 May 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 24 to 60 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Age ≥24 months and ≤60 months adjusted age at the time of enrollment.
- Diagnosis: Unilateral or bilateral hypertonic cerebral palsy secondary to in utero or perinatal stroke/hemorrhage, hypoxic ischemic encephalopathy (including, but not limited to, birth asphyxia), and/or periventricular leukomalacia.
- Performance status: Gross Motor Function Classification Score levels I - IV
- Review of brain imaging (obtained as standard of care prior to study entry) does not suggest a genetic condition or brain malformation.
- Legal authorized representative consent.
Who cannot join
- Available qualified autologous cord blood unit.
- Hypotonic or ataxic cerebral palsy without spasticity.
- Autism and autistic spectrum disorders.
- Hypsarrhythmia.
- Legally blind
- Intractable seizures causing epileptic encephalopathy.
Show all 15Show fewer
- Evidence of a progressive neurologic disease.
- Has an active, uncontrolled systemic infection or documentation of HIV+ status.
- Known genetic disease or phenotypic evidence of a genetic disease on physical exam.
- Concurrent genetic or acquired disease or comorbidity(ies) that could require a future allogeneic stem cell transplant.
- Requires ventilatory support, including home ventilator, CPAP, BiPAP, or supplemental oxygen.
- Impaired renal or liver function as determined by serum creatinine >1.5mg/dL and/or total bilirubin >1.3mg/dL except in patients with known Gilbert's disease.
- Possible immunosuppression, defined as WBC <3,000 cells/mL or absolute lymphocyte count (ALC) <1500 with abnormal T-cell subsets.
- Patient's medical condition does not permit safe travel.
- Previously received any form of cellular therapy.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27705
About this study
Official title: A Phase I/II Study of Allogeneic Umbilical Cord Blood and Umbilical Cord Tissue-Derived Mesenchymal Stromal Cell Infusions in Children With Cerebral Palsy
The main purpose of this study is to estimate change in motor function 12 months after treatment with a single dose of allogeneic umbilical cord blood (AlloCB) or repeated doses of umbilical cord tissue-derived mesenchymal stromal cells (hCT-MSC) in children with cerebral palsy. In addition, this study will contribute much needed data to the clinical trials community on the natural history of the motor function in CP over short-term (less than 1 year) time periods relevant to the conduct of clinical trials and assess the safety of AlloCB and hCT-MSC infusion in children with cerebral palsy.
Read the detailed description
This study is a phase I/II, prospective, randomized, open-label trial designed to determine the effect size of change in GMFM-66 score in subjects treated with hCT-MSC or allogeneic CB and assess the safety of repeated doses of hCT-MSC in children with cerebral palsy. Children ages 2-5 years with cerebral palsy due to hypoxic ischemic encephalopathy, stroke, or periventricular leukomalacia may be eligible to participate. All participants will ultimately be treated with an allogeneic cell product at some point during the study. Participants will be randomized to one of three arms: (1) the "AlloCB" arm will receive one allogeneic CB infusion at the baseline visit; (2) the "MSC" arm will receive three hCT-MSC infusions, one each at baseline, three months, and six months; (3) the "natural history" arm will not receive an infusion at baseline but will receive an allogeneic CB infusion at 12 months. Motor outcome measures will be assessed at baseline, six-months, and one-year time points. Safety will be evaluated at each infusion visit and remotely for an additional 12 months after the final visit. Duration of study participation will be 24 months from the time of baseline visit. Randomization to treatment arms will be stratified by GMFCS level at study entry and etiology of CP (Stroke vs. Other).
- Conditions
- Cerebral Palsy
- Being tested
- Infusion of allogeneic umbilical cord blood, Infusion of MSCs
- Keywords
- CP, Cerebral Palsy, Stem Cell, Cord Blood, MSCs
- Medical subject headings
- Cerebral Palsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Infusion of allogeneic umbilical cord bloodBiological
Subjects will receive a single infusion of allogeneic umbilical cord blood at the baseline visit.
Infusion of MSCsBiological
Subjects will receive 3 infusions of MSCs (baseline, 3 months and 6 months).
| Study group | Role | What they receive |
|---|---|---|
| Allogeneic Umbilical Cord Blood | Experimental | Subjects will receive a single intravenous infusion of a maximum of 10x107/kg allogeneic umbilical cord blood (CB) cells Receives: Biological: Infusion of allogeneic umbilical cord blood |
| Cord Tissue Mesenchymal Stromal Cells | Experimental | Subjects will receive three intravenous infusions of 2x106/kg human umbilical cord tissue cells (hCT-MSC), manufactured from allogeneic umbilical cord donors Receives: Biological: Infusion of MSCs |
| Natural History | Active comparator | Subjects will not receive any study product infusion until after the 12 month assessment. At the 12 month visit, they will receive an infusion of allogeneic umbilical cord blood cells so that all study participants will receive some type of cellular therapy. Receives: Biological: Infusion of allogeneic umbilical cord blood |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Gross Motor Function Measure (GMFM-66) in Excess of Expected Change
GMFM-66 is used to evaluate gross motor function in children with cerebral palsy and is scored using a propriety software program called the Gross Motor Ability Estimator that produces an interval level continuous score ranging from 0 to 100. Higher scores indicate better motor function. The primary endpoint in this study was computed from the GMFM-66 score in three steps: 1) The "observed" change in motor function from Baseline to Month 12 was calculated (positive values indicate improvement, negative values indicate reduction, and zero indicates no change) for each participant; and 2) The expected change in motor function was determined for each participant based on published growth curves; and 3) The expected change in GMFM-66 was subtracted from the observed change to yield the final primary outcome. Positive values indicate a greater change than would be expected, zero indicates change as expected, and negative values indicate a smaller amount of change than would be expected.
Measured: Baseline to 12 months
Secondary outcomes (1)
Number of Adverse Events
The secondary endpoint of this study is the number of adverse events occurring over a 12-month period post-treatment with hCT-MSC or AlloCB.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2018
- Study start10 Apr 2018
- Primary completion26 Feb 2020
- Study completion31 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cerebral 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
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 91 participants (actual)
Sponsor and investigators
- Lead sponsor
- Joanne Kurtzberg, MD
- Sponsor type
- University, hospital or other
- Collaborators
- The Marcus Foundation
- Responsible party
- Sponsor-investigator, Joanne Kurtzberg, MD, Duke University
- Investigators
- Joanne Kurtzberg, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03473301
- Sponsor's protocol ID
- Pro00089362
- Acronym
- ACCeNT-CP
- Status last verified
- Aug 2021
- First submitted
- 15 Mar 2018
- Last updated
- 19 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Liu J, Poehlein E, Chow SC. Statistical Evaluation of Responder Analysis in Stem Cell Clinical Trials. Ther Innov Regul Sci. 2023 Nov;57(6):1238-1247. doi: 10.1007/s43441-023-00556-8. Epub 2023 Aug 9.
PubMed 37555886Sun JM, Case LE, McLaughlin C, Burgess A, Skergan N, Crane S, Jasien JM, Mikati MA, Troy J, Kurtzberg J. Motor function and safety after allogeneic cord blood and cord tissue-derived mesenchymal stromal cells in cerebral palsy: An open-label, randomized trial. Dev Med Child Neurol. 2022 Dec;64(12):1477-1486. doi: 10.1111/dmcn.15325. Epub 2022 Jul 10.
PubMed 35811372
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of Allogeneic Umbilical Cord Blood and Umbilical Cord Tissue-Derived Mesenchymal Stromal Cell Infusions in Children With Cerebral Palsy
- ClinicalTrials.gov ID
- NCT03473301
- Acronym / sponsor ID
- ACCeNT-CP / Pro00089362
- Conditions
- Cerebral Palsy
- Keywords
- CP, Cerebral Palsy, Stem Cell, Cord Blood, MSCs
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 91 participants (actual)
- Lead sponsor
- Joanne Kurtzberg, MDUniversity, hospital or other
- Collaborators
- The Marcus Foundation
- Study start
- 10 Apr 2018 (actual)
- Primary completion
- 26 Feb 2020 (actual)
- Study completion
- 31 May 2021 (actual)
- First posted
- 22 Mar 2018 (actual)
- Results
- Posted 17 Feb 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main purpose of this study is to estimate change in motor function 12 months after treatment with a single dose of allogeneic umbilical cord blood (AlloCB) or repeated doses of umbilical cord tissue-derived mesenchymal stromal cells (hCT-MSC) in children with cerebral palsy. In addition, this study will contribute much needed data to the clinical trials community on the natural history of the motor function in CP over short-term (less than 1 year) time periods relevant to the conduct of clinical trials and assess the safety of AlloCB and hCT-MSC infusion in children with cerebral palsy.
Detailed description
This study is a phase I/II, prospective, randomized, open-label trial designed to determine the effect size of change in GMFM-66 score in subjects treated with hCT-MSC or allogeneic CB and assess the safety of repeated doses of hCT-MSC in children with cerebral palsy. Children ages 2-5 years with cerebral palsy due to hypoxic ischemic encephalopathy, stroke, or periventricular leukomalacia may be eligible to participate. All participants will ultimately be treated with an allogeneic cell product at some point during the study. Participants will be randomized to one of three arms: (1) the "AlloCB" arm will receive one allogeneic CB infusion at the baseline visit; (2) the "MSC" arm will receive three hCT-MSC infusions, one each at baseline, three months, and six months; (3) the "natural history" arm will not receive an infusion at baseline but will receive an allogeneic CB infusion at 12 months. Motor outcome measures will be assessed at baseline, six-months, and one-year time points. Safety will be evaluated at each infusion visit and remotely for an additional 12 months after the final visit. Duration of study participation will be 24 months from the time of baseline visit. Randomization to treatment arms will be stratified by GMFCS level at study entry and etiology of CP (Stroke vs. Other).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Allogeneic Umbilical Cord Blood | Experimental | Biological: Infusion of allogeneic umbilical cord bloodSubjects will receive a single intravenous infusion of a maximum of 10x107/kg allogeneic umbilical cord blood (CB) cells |
| Cord Tissue Mesenchymal Stromal Cells | Experimental | Biological: Infusion of MSCsSubjects will receive three intravenous infusions of 2x106/kg human umbilical cord tissue cells (hCT-MSC), manufactured from allogeneic umbilical cord donors |
| Natural History | Active comparator | Biological: Infusion of allogeneic umbilical cord bloodSubjects will not receive any study product infusion until after the 12 month assessment. At the 12 month visit, they will receive an infusion of allogeneic umbilical cord blood cells so that all study participants will receive some type of cellular therapy. |
Who may qualify
- Ages
- 24 to 60 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Age ≥24 months and ≤60 months adjusted age at the time of enrollment.
- Diagnosis: Unilateral or bilateral hypertonic cerebral palsy secondary to in utero or perinatal stroke/hemorrhage, hypoxic ischemic encephalopathy (including, but not limited to, birth asphyxia), and/or periventricular leukomalacia.
- Performance status: Gross Motor Function Classification Score levels I - IV
- Review of brain imaging (obtained as standard of care prior to study entry) does not suggest a genetic condition or brain malformation.
- Legal authorized representative consent.
Key exclusion criteria (15 listed)
- Available qualified autologous cord blood unit.
- Hypotonic or ataxic cerebral palsy without spasticity.
- Autism and autistic spectrum disorders.
- Hypsarrhythmia.
- Legally blind
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 |
|---|---|---|
| Infusion of allogeneic umbilical cord bloodSubjects will receive a single infusion of allogeneic umbilical cord blood at the baseline visit. | Biological | Allogeneic Umbilical Cord Blood, Natural History |
| Infusion of MSCsSubjects will receive 3 infusions of MSCs (baseline, 3 months and 6 months). | Biological | Cord Tissue Mesenchymal Stromal Cells |
Primary outcome
Change in Gross Motor Function Measure (GMFM-66) in Excess of Expected Change
Time frame: Baseline to 12 months
GMFM-66 is used to evaluate gross motor function in children with cerebral palsy and is scored using a propriety software program called the Gross Motor Ability Estimator that produces an interval level continuous score ranging from 0 to 100. Higher scores indicate better motor function. The primary endpoint in this study was computed from the GMFM-66 score in three steps: 1) The "observed" change in motor function from Baseline to Month 12 was calculated (positive values indicate improvement, negative values indicate reduction, and zero indicates no change) for each participant; and 2) The expected change in motor function was determined for each participant based on published growth curves; and 3) The expected change in GMFM-66 was subtracted from the observed change to yield the final primary outcome. Positive values indicate a greater change than would be expected, zero indicates change as expected, and negative values indicate a smaller amount of change than would be expected.
1 secondary outcome
Number of Adverse Events
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37555886Liu J, Poehlein E, Chow SC. Statistical Evaluation of Responder Analysis in Stem Cell Clinical Trials. Ther Innov Regul Sci. 2023 Nov;57(6):1238-1247. doi: 10.1007/s43441-023-00556-8. Epub 2023 Aug 9.
- Derived from this study: PubMed 35811372Sun JM, Case LE, McLaughlin C, Burgess A, Skergan N, Crane S, Jasien JM, Mikati MA, Troy J, Kurtzberg J. Motor function and safety after allogeneic cord blood and cord tissue-derived mesenchymal stromal cells in cerebral palsy: An open-label, randomized trial. Dev Med Child Neurol. 2022 Dec;64(12):1477-1486. doi: 10.1111/dmcn.15325. Epub 2022 Jul 10.
- Individual participant dataSharing planned: No
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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.
Joanne Kurtzberg, MD principal investigator
Duke University
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 Infusion of allogeneic umbilical cord blood and Infusion of MSCs in people with Cerebral Palsy, run by Joanne Kurtzberg, MD at 1 site in United States.
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 5 inclusion and 15 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 19 Aug 2021. 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 United States. 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. 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?
Yes. Results are posted in the registry (first posted 17 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 Gross Motor Function Measure (GMFM-66) in Excess of Expected Change (time frame: Baseline to 12 months). 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 NCT03473301, which also lists 2 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 19 Aug 2021.