Hypoxia-Ischemia, BrainPhase 1SHIELDNCT04261335
The Clinical Trial of CL2020 Cells for Neonatal Hypoxic Ischemic Encephalopathy
A Phase 1 study testing CL2020 cells in people with Hypoxia-Ischemia, Brain, run by Nagoya University at 1 site in Japan.
Trial summary
The purpose of this study is to evaluate the safety and the tolerability of CL2020 cells in hypoxic ischemic encephalopathy neonates with hypothermia therapy. In addition, we will evaluate the efficacy of CL2020 cells for infant development. Read more about this study
- Who is it for?
- Ages 4 to 14 days
- Conditions the study is for
- Hypoxia-Ischemia, Brain
- What is being tested?
- CL2020 cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteJapan
- Study dates
- 4 Mar 2020to 12 Dec 2022
- Phase
- Phase 1
- 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 4 to 14 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- At least 36 weeks gestation, and either one of the following criteria (i.-iii.) i. Apgar score ≤5 at 10 minutes ii. Continued resuscitation for at least 10 minutes iii. pH <7.0 or base deficit ≥16 mmol/L in any blood sample obtained within 60 min of birth
- Moderate or severe encephalopathy by a Sarnat criteria
- Undergone therapeutic hypothermia started before six hours of birth, and done for 72 hours continuously
- Birth weight ≥1,800 g
- Heart rate ≥100/min, and SpO2 ≥90 %
- Able to provide voluntary written consent after receiving adequate information about the study (consent will be obtained from an acceptable representative)
Who cannot join
- Suspected or confirmed severe congenital abnormalities or chromosomal anomaly
- Planned to undergo surgery or radiation therapy
- Scheduled to take systemic corticosteroids treatment for over five days
- Blood glucose ≥ 200 mg/dL
- Participation in another clinical study (not exclude patients in observational studies)
- Suspected or confirmed active and severe infection
Show all 9Show fewer
- Positive for HBs antigen, HCV antibody, HIV antibody, HTLV-1 antibody or syphilis serum reaction
- History of severe hypersensitivity or anaphylactic reaction
- Severe complications
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Evaluation of Safety and Tolerability of CL2020 in Neonatal Hypoxic Ischemic Encephalopathy Patients With Therapeutic Hypothermia in the Dose Escalation Clinical Trial
The purpose of this study is to evaluate the safety and the tolerability of CL2020 cells in hypoxic ischemic encephalopathy neonates with hypothermia therapy. In addition, we will evaluate the efficacy of CL2020 cells for infant development.
- Conditions
- Hypoxia-Ischemia, Brain
- Being tested
- CL2020 cells
- Keywords
- Hypoxia-Ischemia, Brain, Infant, Newborn, Mesenchymal Stem Cells
- Medical subject headings
- Hypoxia-Ischemia, Brain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CL2020 cellsBiological
1.5 million or 15 million cells, IV on day 5 to 14 of birth
| Study group | Role | What they receive |
|---|---|---|
| CL2020 cells | Experimental | Intravenous injection of CL2020 cells Receives: Biological: CL2020 cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events
Any adverse events are summarized.
Measured: until 12 weeks after the administration
Secondary outcomes (12)
Incidence of composite endpoints (death, continuous respiratory support, and continuous use of vasopressors or pulmonary vasodilators)
Incidence of composite endpoints is summarized.
Measured: at 12, 26, 38, 52, and 78 weeks after administration
Mortality
Mortality is summarized.
Measured: all of the clinical trial period (up to 44 months)
Overall survival
Overall survival is summarized.
Measured: all of the clinical trial period (up to 44 months)
Duration of continuous respiratory support
Duration of continuous respiratory support is summarized.
Measured: up to 78 weeks
Duration of continuous use of vasopressors or pulmonary vasodilators
Duration of continuous use of vasopressors or pulmonary vasodilators is summarized.
Measured: up to 78 weeks
The composite score of cognitive scale, language scale, motor scale, social-emotional scale, and adaptive behavior scale in Bayley Scales of Infant and Toddler Development Third edition
Each composite scores are summarized. The higher scores mean a better outcome.
Measured: 78 weeks after administration
The developmental quotient in Kyoto Scale of Psychological Development 2001
The developmental quotient is summarized. The higher scores mean a better outcome.
Measured: 78 weeks after administration
Presence of 1) head control, 2) roll over, 3) sitting position, 4) crawl, 5) independent gait, and 6) meaningful words
Presence of each event is summarized.
Measured: at 26, 38, 52, and 78weeks after administration
Presence of spasticity
Presence of spasticity is summarized. Spasticity is the condition as below: increased muscle tone, or increased deep tendon reflex.
Measured: at 12, 26, 38, 52, and 78 weeks after administration
Presence of epilepsy
Presence of spasticity is summarized. The definition of epilepsy is the condition based on the International League Against Epilepsy.
Measured: until 78 weeks after administration
MRI score
MRI score is summarized. The scoring system is based on the report of Barkovich AJ, et al. (AJNR Am J Neuroradiol. 1998 ;19(1):143-9.) . The higher scores mean a worse outcome.
Measured: at 2, and 78 weeks after administration
Gross Motor Function Classification System (GMFCS) score
GMFCS score is summarized. The gross motor function can be categorized into 5 different level. The higher scores mean a worse outcome.
Measured: at 78 weeks after administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2020
- Study start4 Mar 2020
- Primary completion29 Sep 2021
- Study completion12 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hypoxia-Ischemia, BrainStudies 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 3 + 3 dose escalation study design
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nagoya University
- Sponsor type
- University, hospital or other
- Collaborators
- Life Science Institute, Inc.
- Responsible party
- Principal investigator, Yoshiaki Sato, Nagoya University
- Investigators
- Yoshiaki Sato, MD, PhD, Principal investigator, Department of Center for Maternal Neonatal Care, Nagoya University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04261335
- Sponsor's protocol ID
- CAMCR-014
- Other IDs
- jRCT2043190112
- Acronym
- SHIELD
- Status last verified
- Sep 2023
- First submitted
- 1 Feb 2020
- Last updated
- 3 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Sato Y, Shimizu S, Ueda K, Suzuki T, Suzuki S, Miura R, Ando M, Tsuda K, Iwata O, Muramatsu Y, Kidokoro H, Hirakawa A, Hayakawa M; SHEILD team. Safety and tolerability of a Muse cell-based product in neonatal hypoxic-ischemic encephalopathy with therapeutic hypothermia (SHIELD trial). Stem Cells Transl Med. 2024 Nov 12;13(11):1053-1066. doi: 10.1093/stcltm/szae071.
PubMed 39401019Matsuyama N, Shimizu S, Ueda K, Suzuki T, Suzuki S, Miura R, Katayama A, Ando M, Mizuno M, Hirakawa A, Hayakawa M, Sato Y. Safety and tolerability of a multilineage-differentiating stress-enduring cell-based product in neonatal hypoxic-ischaemic encephalopathy with therapeutic hypothermia (SHIELD trial): a clinical trial protocol open-label, non-randomised, dose-escalation trial. BMJ Open. 2022 Apr 26;12(4):e057073. doi: 10.1136/bmjopen-2021-057073.
PubMed 35473726
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Evaluation of Safety and Tolerability of CL2020 in Neonatal Hypoxic Ischemic Encephalopathy Patients With Therapeutic Hypothermia in the Dose Escalation Clinical Trial
- ClinicalTrials.gov ID
- NCT04261335
- Acronym / sponsor ID
- SHIELD / CAMCR-014
- Conditions
- Hypoxia-Ischemia, Brain
- Keywords
- Hypoxia-Ischemia, Brain, Infant, Newborn, Mesenchymal Stem Cells
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Nagoya UniversityUniversity, hospital or other
- Collaborators
- Life Science Institute, Inc.
- Study start
- 4 Mar 2020 (actual)
- Primary completion
- 29 Sep 2021 (actual)
- Study completion
- 12 Dec 2022 (actual)
- First posted
- 7 Feb 2020 (actual)
- 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 purpose of this study is to evaluate the safety and the tolerability of CL2020 cells in hypoxic ischemic encephalopathy neonates with hypothermia therapy. In addition, we will evaluate the efficacy of CL2020 cells for infant development.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 3 + 3 dose escalation study design
| Arm | Type | Receives |
|---|---|---|
| CL2020 cells | Experimental | Biological: CL2020 cellsIntravenous injection of CL2020 cells |
Who may qualify
- Ages
- 4 to 14 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- At least 36 weeks gestation, and either one of the following criteria (i.-iii.) i. Apgar score ≤5 at 10 minutes ii. Continued resuscitation for at least 10 minutes iii. pH <7.0 or base deficit ≥16 mmol/L in any blood sample obtained within 60 min of birth
- Moderate or severe encephalopathy by a Sarnat criteria
- Undergone therapeutic hypothermia started before six hours of birth, and done for 72 hours continuously
- Birth weight ≥1,800 g
- Heart rate ≥100/min, and SpO2 ≥90 %
Key exclusion criteria (9 listed)
- Suspected or confirmed severe congenital abnormalities or chromosomal anomaly
- Planned to undergo surgery or radiation therapy
- Scheduled to take systemic corticosteroids treatment for over five days
- Blood glucose ≥ 200 mg/dL
- Participation in another clinical study (not exclude patients in observational studies)
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 |
|---|---|---|
| CL2020 cells1.5 million or 15 million cells, IV on day 5 to 14 of birth | Biological | CL2020 cells |
Primary outcome
Incidence of adverse events
Time frame: until 12 weeks after the administration
Any adverse events are summarized.
12 secondary outcomes
Incidence of composite endpoints (death, continuous respiratory support, and continuous use of vasopressors or pulmonary vasodilators)
Time frame: at 12, 26, 38, 52, and 78 weeks after administration
Mortality
Time frame: all of the clinical trial period (up to 44 months)
Overall survival
Time frame: all of the clinical trial period (up to 44 months)
Duration of continuous respiratory support
Time frame: up to 78 weeks
Duration of continuous use of vasopressors or pulmonary vasodilators
Time frame: up to 78 weeks
The composite score of cognitive scale, language scale, motor scale, social-emotional scale, and adaptive behavior scale in Bayley Scales of Infant and Toddler Development Third edition
Time frame: 78 weeks after administration
The developmental quotient in Kyoto Scale of Psychological Development 2001
Time frame: 78 weeks after administration
Presence of 1) head control, 2) roll over, 3) sitting position, 4) crawl, 5) independent gait, and 6) meaningful words
Time frame: at 26, 38, 52, and 78weeks after administration
Presence of spasticity
Time frame: at 12, 26, 38, 52, and 78 weeks after administration
Presence of epilepsy
Time frame: until 78 weeks after administration
MRI score
Time frame: at 2, and 78 weeks after administration
Gross Motor Function Classification System (GMFCS) score
Time frame: at 78 weeks after administration
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 3 Oct 2023.
- Derived from this study: PubMed 39401019Sato Y, Shimizu S, Ueda K, Suzuki T, Suzuki S, Miura R, Ando M, Tsuda K, Iwata O, Muramatsu Y, Kidokoro H, Hirakawa A, Hayakawa M; SHEILD team. Safety and tolerability of a Muse cell-based product in neonatal hypoxic-ischemic encephalopathy with therapeutic hypothermia (SHIELD trial). Stem Cells Transl Med. 2024 Nov 12;13(11):1053-1066. doi: 10.1093/stcltm/szae071.
- Derived from this study: PubMed 35473726Matsuyama N, Shimizu S, Ueda K, Suzuki T, Suzuki S, Miura R, Katayama A, Ando M, Mizuno M, Hirakawa A, Hayakawa M, Sato Y. Safety and tolerability of a multilineage-differentiating stress-enduring cell-based product in neonatal hypoxic-ischaemic encephalopathy with therapeutic hypothermia (SHIELD trial): a clinical trial protocol open-label, non-randomised, dose-escalation trial. BMJ Open. 2022 Apr 26;12(4):e057073. doi: 10.1136/bmjopen-2021-057073.
- 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.
Yoshiaki Sato, MD, PhD principal investigator
Department of Center for Maternal Neonatal Care, Nagoya University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CL2020 cells in people with Hypoxia-Ischemia, Brain, run by Nagoya University at 1 site in Japan.
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 6 inclusion and 9 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 3 Oct 2023. 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 Japan. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Incidence of adverse events (time frame: until 12 weeks after the administration). 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 NCT04261335, 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 3 Oct 2023.