A Study of UCB and MSCs in Children With CP: ACCeNT-CP

• Sponsor: Joanne Kurtzberg, MD (Other)
• Overall Status: Completed
• CT.gov ID: NCT03473301
• Collaborator: The Marcus Foundation (Other)
• Enrollment: 91
• Location: 1
• Arms: 3
• Actual Duration (Months): 37.7
• Patients Per Site Per Month: 2.4

Study Details

Study Description

Brief 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. 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.

Condition or Disease	Intervention/Treatment	Phase
Cerebral Palsy	Biological: Infusion of allogeneic umbilical cord blood; Biological: Infusion of MSCs	Phase 1/Phase 2

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

• Study Type: Interventional
• Actual Enrollment: 91 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Masking Description: Every attempt will be made to blind the outcomes assessor.
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Apr 10, 2018
• Actual Primary Completion Date: Feb 26, 2020
• Actual Study Completion Date: May 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Allogeneic Umbilical Cord Blood Subjects will receive a single intravenous infusion of a maximum of 10x107/kg allogeneic umbilical cord blood (CB) cells	Biological: Infusion of allogeneic umbilical cord blood; Subjects will receive a single infusion of allogeneic umbilical cord blood at the baseline visit.
Experimental: Cord Tissue Mesenchymal Stromal Cells Subjects will receive three intravenous infusions of 2x106/kg human umbilical cord tissue cells (hCT-MSC), manufactured from allogeneic umbilical cord donors	Biological: Infusion of MSCs; Subjects will receive 3 infusions of MSCs (baseline, 3 months and 6 months).
Active Comparator: Natural History 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.	Biological: Infusion of allogeneic umbilical cord blood; Subjects will receive a single infusion of allogeneic umbilical cord blood at the baseline visit.

Outcome Measures

Primary Outcome Measures

1. Change in Gross Motor Function Measure (GMFM-66) in Excess of Expected Change [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.

Secondary Outcome Measures

1. Number of Adverse Events [12 months]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 24 Months to 60 Months
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Age ≥24 months and ≤60 months adjusted age at the time of enrollment.

2. 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.

3. Performance status: Gross Motor Function Classification Score levels I - IV

4. Review of brain imaging (obtained as standard of care prior to study entry) does not suggest a genetic condition or brain malformation.

5. Legal authorized representative consent.

Exclusion Criteria:

1. Available qualified autologous cord blood unit.

2. Hypotonic or ataxic cerebral palsy without spasticity.

3. Autism and autistic spectrum disorders.

4. Hypsarrhythmia.

5. Legally blind

6. Intractable seizures causing epileptic encephalopathy.

7. Evidence of a progressive neurologic disease.

8. Has an active, uncontrolled systemic infection or documentation of HIV+ status.

9. Known genetic disease or phenotypic evidence of a genetic disease on physical exam.

10. Concurrent genetic or acquired disease or comorbidity(ies) that could require a future allogeneic stem cell transplant.

11. Requires ventilatory support, including home ventilator, CPAP, BiPAP, or supplemental oxygen.

12. 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.

13. Possible immunosuppression, defined as WBC <3,000 cells/mL or absolute lymphocyte count (ALC) <1500 with abnormal T-cell subsets.

14. Patient's medical condition does not permit safe travel.

15. Previously received any form of cellular therapy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Duke University Medical Center	Durham	North Carolina	United States	27705

Sponsors and Collaborators

• Joanne Kurtzberg, MD
• The Marcus Foundation

Investigators

• Principal Investigator: Joanne Kurtzberg, MD, Duke University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 1, 2019

More Information

Publications

None provided.

• Responsible Party: Joanne Kurtzberg, MD, MD, Duke University
• ClinicalTrials.gov Identifier: NCT03473301
• Other Study ID Numbers: Pro00089362
• First Posted: Mar 22, 2018
• Last Update Posted: Aug 19, 2021
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Joanne Kurtzberg, MD, MD, Duke University: CP; Cerebral Palsy; Stem Cell; Cord Blood; MSCs
• Additional relevant MeSH terms: Cerebral Palsy

Study Results

Participant Flow

Recruitment Details	First participant randomized on April 10, 2018. Last participant randomized May 30, 2019. Single center study.

Arm/Group Title	Allogeneic Umbilical Cord Blood (AlloCB)	Cord Tissue Mesenchymal Stromal Cells (MSC)	Natural History, Then AlloCB
Arm/Group Description	Subjects will receive a single intravenous infusion of a maximum of 10x107/kg allogeneic umbilical cord blood (CB) cells Infusion of allogeneic umbilical cord blood: Subjects will receive a single infusion of allogeneic umbilical cord blood at the baseline visit.	Subjects will receive three intravenous infusions of 2x106/kg human umbilical cord tissue cells (hCT-MSC), manufactured from allogeneic umbilical cord donors Infusion of MSCs: Subjects will receive 3 infusions of MSCs (baseline, 3 months and 6 months).	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. Infusion of allogeneic umbilical cord blood: Subjects will receive a single infusion of allogeneic umbilical cord blood at the baseline visit.
Period Title: Overall Study
STARTED	31	29	31
COMPLETED	20	23	25
NOT COMPLETED	11	6	6

Baseline Characteristics

Arm/Group Title	Allogeneic Umbilical Cord Blood (AlloCB)	Cord Tissue Mesenchymal Stromal Cells (MSC)	Natural History, Then AlloCB	Total
Arm/Group Description	Subjects will receive a single intravenous infusion of a maximum of 10x107/kg allogeneic umbilical cord blood (CB) cells Infusion of allogeneic umbilical cord blood: Subjects will receive a single infusion of allogeneic umbilical cord blood at the baseline visit.	Subjects will receive three intravenous infusions of 2x106/kg human umbilical cord tissue cells (hCT-MSC), manufactured from allogeneic umbilical cord donors Infusion of MSCs: Subjects will receive 3 infusions of MSCs (baseline, 3 months and 6 months).	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. Infusion of allogeneic umbilical cord blood: Subjects will receive a single infusion of allogeneic umbilical cord blood at the baseline visit.	Total of all reporting groups
Overall Participants	31	29	31	91
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	3.47 (0.96)	3.53 (0.88)	3.55 (0.84)	3.52 (0.89)
Sex: Female, Male (Count of Participants)
Female	16 51.6%	9 31%	14 45.2%	39 42.9%
Male	15 48.4%	20 69%	17 54.8%	52 57.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 12.9%	2 6.9%	6 19.4%	12 13.2%
Not Hispanic or Latino	27 87.1%	27 93.1%	25 80.6%	79 86.8%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
Asian	0 0%	3 10.3%	3 9.7%	6 6.6%
British Indian	0 0%	0 0%	1 3.2%	1 1.1%
Italian	0 0%	0 0%	1 3.2%	1 1.1%
White	30 96.8%	25 86.2%	24 77.4%	79 86.8%
More than one race	1 3.2%	1 3.4%	2 6.5%	4 4.4%
Region of Enrollment (Count of Participants)
United States	31 100%	29 100%	31 100%	91 100%

Outcome Measures

1. Primary Outcome

Title	Change in Gross Motor Function Measure (GMFM-66) in Excess of Expected Change
Description	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.
Time Frame	Baseline to 12 months

Outcome Measure Data

Analysis Population Description

Efficacy data not collected on Natural History participants after receiving allogeneic umbilical cord blood. Participants who did not complete the Month 12 visit are excluded.

Arm/Group Title	Allogeneic Umbilical Cord Blood (AlloCB)	Cord Tissue Mesenchymal Stromal Cells (MSC)	Natural History	AlloCB After Natural History
Arm/Group Description	Subjects will receive a single intravenous infusion of a maximum of 10x107/kg allogeneic umbilical cord blood (CB) cells Infusion of allogeneic umbilical cord blood: Subjects will receive a single infusion of allogeneic umbilical cord blood at the baseline visit.	Subjects will receive three intravenous infusions of 2x106/kg human umbilical cord tissue cells (hCT-MSC), manufactured from allogeneic umbilical cord donors Infusion of MSCs: Subjects will receive 3 infusions of MSCs (baseline, 3 months and 6 months).	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. Infusion of allogeneic umbilical cord blood: Subjects will receive a single infusion of allogeneic umbilical cord blood at the baseline visit.	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. Infusion of allogeneic umbilical cord blood: Subjects will receive a single infusion of allogeneic umbilical cord blood at the baseline visit.
Measure Participants	20	23	25	0
Mean (95% Confidence Interval) [score on a scale]	5.83	4.27	3.15

2. Secondary Outcome

Title	Number of Adverse Events
Description	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.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Four participants randomized to the Natural History arm did not receive an infusion of AlloCB at Month12.

Arm/Group Title	Allogeneic Umbilical Cord Blood (AlloCB)	Cord Tissue Mesenchymal Stromal Cells (MSC)	Natural History	AlloCB After Natural History
Arm/Group Description	Subjects will receive a single intravenous infusion of a maximum of 10x107/kg allogeneic umbilical cord blood (CB) cells Infusion of allogeneic umbilical cord blood: Subjects will receive a single infusion of allogeneic umbilical cord blood at the baseline visit.	Subjects will receive three intravenous infusions of 2x106/kg human umbilical cord tissue cells (hCT-MSC), manufactured from allogeneic umbilical cord donors Infusion of MSCs: Subjects will receive 3 infusions of MSCs (baseline, 3 months and 6 months).	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. Infusion of allogeneic umbilical cord blood: Subjects will receive a single infusion of allogeneic umbilical cord blood at the baseline visit.	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. Infusion of allogeneic umbilical cord blood: Subjects will receive a single infusion of allogeneic umbilical cord blood at the baseline visit.
Measure Participants	31	29	31	27
Number [adverse events]	30	48	16	9

Adverse Events

Time Frame	12 months
Arm/Group Title	Allogeneic Umbilical Cord Blood (AlloCB)		Cord Tissue Mesenchymal Stromal Cells (MSC)		Natural History		AlloCB After Natural History
Arm/Group Description	Subjects will receive a single intravenous infusion of a maximum of 10x107/kg allogeneic umbilical cord blood (CB) cells Infusion of allogeneic umbilical cord blood: Subjects will receive a single infusion of allogeneic umbilical cord blood at the baseline visit.		Subjects will receive three intravenous infusions of 2x106/kg human umbilical cord tissue cells (hCT-MSC), manufactured from allogeneic umbilical cord donors Infusion of MSCs: Subjects will receive 3 infusions of MSCs (baseline, 3 months and 6 months).		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. Infusion of allogeneic umbilical cord blood: Subjects will receive a single infusion of allogeneic umbilical cord blood at the baseline visit.		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. Infusion of allogeneic umbilical cord blood: Subjects will receive a single infusion of allogeneic umbilical cord blood at the baseline visit.
All Cause Mortality
	Allogeneic Umbilical Cord Blood (AlloCB)		Cord Tissue Mesenchymal Stromal Cells (MSC)		Natural History		AlloCB After Natural History
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/31 (0%)		0/29 (0%)		0/31 (0%)		0/27 (0%)
Serious Adverse Events
	Allogeneic Umbilical Cord Blood (AlloCB)		Cord Tissue Mesenchymal Stromal Cells (MSC)		Natural History		AlloCB After Natural History
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/31 (29%)		3/29 (10.3%)		9/31 (29%)		3/27 (11.1%)
Gastrointestinal disorders
Gastritis	1/31 (3.2%)		0/29 (0%)		0/31 (0%)		0/27 (0%)
Infections and infestations
Bronchitis viral	1/31 (3.2%)		0/29 (0%)		0/31 (0%)		0/27 (0%)
Respiratory syncytial virus infection	1/31 (3.2%)		0/29 (0%)		0/31 (0%)		0/27 (0%)
Respiratory tract infection viral	0/31 (0%)		0/29 (0%)		1/31 (3.2%)		0/27 (0%)
Rhinovirus infection	1/31 (3.2%)		0/29 (0%)		0/31 (0%)		0/27 (0%)
Metabolism and nutrition disorders
Dehydration	1/31 (3.2%)		0/29 (0%)		0/31 (0%)		0/27 (0%)
Nervous system disorders
Seizure	2/31 (6.5%)		0/29 (0%)		5/31 (16.1%)		1/27 (3.7%)
Psychiatric disorders
Sleep disorder	0/31 (0%)		1/29 (3.4%)		0/31 (0%)		0/27 (0%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure	0/31 (0%)		0/29 (0%)		1/31 (3.2%)		0/27 (0%)
Surgical and medical procedures
Hospitalisation	0/31 (0%)		2/29 (6.9%)		2/31 (6.5%)		2/27 (7.4%)
Surgery	3/31 (9.7%)		0/29 (0%)		1/31 (3.2%)		0/27 (0%)
Tonsillectomy	0/31 (0%)		0/29 (0%)		1/31 (3.2%)		0/27 (0%)
Other (Not Including Serious) Adverse Events
	Allogeneic Umbilical Cord Blood (AlloCB)		Cord Tissue Mesenchymal Stromal Cells (MSC)		Natural History		AlloCB After Natural History
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/31 (58.1%)		22/29 (75.9%)		12/31 (38.7%)		6/27 (22.2%)
Blood and lymphatic system disorders
Thrombocytopenia	0/31 (0%)		0/29 (0%)		1/31 (3.2%)		0/27 (0%)
Anaemia	0/31 (0%)		1/29 (3.4%)		0/31 (0%)		0/27 (0%)
Cardiac disorders
Bradycardia	0/31 (0%)		0/29 (0%)		1/31 (3.2%)		0/27 (0%)
Ear and labyrinth disorders
Hypoacusis	1/31 (3.2%)		0/29 (0%)		0/31 (0%)		0/27 (0%)
Gastrointestinal disorders
Gastroesophageal reflux disease	0/31 (0%)		0/29 (0%)		1/31 (3.2%)		0/27 (0%)
Cyclic vomiting syndrome	0/31 (0%)		0/29 (0%)		0/31 (0%)		1/27 (3.7%)
Toothache	0/31 (0%)		0/29 (0%)		0/31 (0%)		1/27 (3.7%)
Constipation	1/31 (3.2%)		0/29 (0%)		0/31 (0%)		0/27 (0%)
Diarrhoea	1/31 (3.2%)		1/29 (3.4%)		0/31 (0%)		0/27 (0%)
Vomiting	1/31 (3.2%)		2/29 (6.9%)		0/31 (0%)		0/27 (0%)
General disorders
Pyrexia	2/31 (6.5%)		3/29 (10.3%)		2/31 (6.5%)		1/27 (3.7%)
Fatigue	1/31 (3.2%)		0/29 (0%)		0/31 (0%)		0/27 (0%)
Influenza like illness	0/31 (0%)		1/29 (3.4%)		0/31 (0%)		0/27 (0%)
Infusion site rash	0/31 (0%)		1/29 (3.4%)		0/31 (0%)		0/27 (0%)
Injection site reaction	0/31 (0%)		1/29 (3.4%)		0/31 (0%)		0/27 (0%)
Immune system disorders
Anaphylactic reaction	1/31 (3.2%)		0/29 (0%)		0/31 (0%)		0/27 (0%)
Drug hypersensitivity	0/31 (0%)		1/29 (3.4%)		0/31 (0%)		0/27 (0%)
Infections and infestations
Bronchitis	0/31 (0%)		0/29 (0%)		1/31 (3.2%)		0/27 (0%)
Enterocolitis infectious	0/31 (0%)		0/29 (0%)		1/31 (3.2%)		0/27 (0%)
Otitis media	2/31 (6.5%)		2/29 (6.9%)		1/31 (3.2%)		0/27 (0%)
Hand-foot-and-mouth disease	2/31 (6.5%)		0/29 (0%)		0/31 (0%)		0/27 (0%)
Influenza	1/31 (3.2%)		0/29 (0%)		0/31 (0%)		0/27 (0%)
Pneumonia	1/31 (3.2%)		0/29 (0%)		0/31 (0%)		0/27 (0%)
Upper respiratory tract infection	1/31 (3.2%)		8/29 (27.6%)		0/31 (0%)		0/27 (0%)
Tonsillitis	0/31 (0%)		1/29 (3.4%)		0/31 (0%)		0/27 (0%)
Varicella	0/31 (0%)		1/29 (3.4%)		0/31 (0%)		0/27 (0%)
Injury, poisoning and procedural complications
Fall	2/31 (6.5%)		1/29 (3.4%)		1/31 (3.2%)		0/27 (0%)
Fracture	0/31 (0%)		0/29 (0%)		1/31 (3.2%)		0/27 (0%)
Infusion related reaction	1/31 (3.2%)		4/29 (13.8%)		0/31 (0%)		2/27 (7.4%)
Arthropod bite	1/31 (3.2%)		0/29 (0%)		0/31 (0%)		0/27 (0%)
Tooth avulsion	1/31 (3.2%)		0/29 (0%)		0/31 (0%)		0/27 (0%)
Investigations
Laboratory test abnormal	2/31 (6.5%)		0/29 (0%)		0/31 (0%)		0/27 (0%)
Metabolism and nutrition disorders
Dehydration	1/31 (3.2%)		0/29 (0%)		0/31 (0%)		0/27 (0%)
Nervous system disorders
Nervous system disorder	0/31 (0%)		0/29 (0%)		1/31 (3.2%)		0/27 (0%)
Seizure	0/31 (0%)		6/29 (20.7%)		2/31 (6.5%)		0/27 (0%)
Headache	0/31 (0%)		2/29 (6.9%)		0/31 (0%)		1/27 (3.7%)
Facial paresis	1/31 (3.2%)		0/29 (0%)		0/31 (0%)		0/27 (0%)
Partial seizures	1/31 (3.2%)		0/29 (0%)		0/31 (0%)		0/27 (0%)
Disturbance in attention	0/31 (0%)		1/29 (3.4%)		0/31 (0%)		0/27 (0%)
Psychiatric disorders
Insomnia	0/31 (0%)		1/29 (3.4%)		0/31 (0%)		0/27 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/31 (0%)		0/29 (0%)		0/31 (0%)		1/27 (3.7%)
Skin and subcutaneous tissue disorders
Rash	0/31 (0%)		4/29 (13.8%)		0/31 (0%)		1/27 (3.7%)
Henoch-Schonlein purpura	0/31 (0%)		1/29 (3.4%)		0/31 (0%)		0/27 (0%)
Rash maculo-papular	0/31 (0%)		2/29 (6.9%)		0/31 (0%)		0/27 (0%)
Urticaria	0/31 (0%)		1/29 (3.4%)		0/31 (0%)		0/27 (0%)
Surgical and medical procedures
Adenotonsillectomy	0/31 (0%)		0/29 (0%)		1/31 (3.2%)		0/27 (0%)
Strabismus correction	1/31 (3.2%)		0/29 (0%)		2/31 (6.5%)		0/27 (0%)
Dental operation	1/31 (3.2%)		0/29 (0%)		0/31 (0%)		0/27 (0%)
Orchidopexy	1/31 (3.2%)		1/29 (3.4%)		0/31 (0%)		0/27 (0%)
Suture insertion	1/31 (3.2%)		0/29 (0%)		0/31 (0%)		0/27 (0%)
Tongue tie operation	1/31 (3.2%)		0/29 (0%)		0/31 (0%)		0/27 (0%)
Adenoidectomy	0/31 (0%)		1/29 (3.4%)		0/31 (0%)		0/27 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.