Precursor Preference in Surfactant Synthesis of Newborns

1
Precursor Preference in Surfactant Synthesis of
Newborns

• Sarah Frankel, PhD
• Human Studies Committee
• Washington University
• School of Medicine

2
Inclusion Criteria

• Controls
• Full term infants with normal lungs that are
  viable
  
• Are in the NICU
• Require mechanical ventilation for breathing
  difficulties caused by illness other than lung
  disease
  
• Infants with lung disease
• 28 weeks or less at birth
• Up to 6 weeks old after birth

3
Exclusion Criteria

• Infants for whom death is imminent
• Non-viable infants
• Those with known infections
• Infants with congenital anomalies and pulmonary
  hemorrhage

4
Rationale for Inclusion/Exclusion Criteria

• Preliminary data indicates that kinetic
  parameters of surfactant metabolism evolve with
  infants age
  
• To determine impact of age vs. worsening chronic
  lung disease need to study surfactant metabolism
  in infants without lung disease

5
Research Procedures

• 24 hour continuous infusion of non-radioactive
  stable isotopes 1-13C1 acetate and 1,2,3,4
  13C4 palmitate.

6
Research Procedures

• 2.5 ml blood draw done in 5 - 0.5 ml increments
  over the first 27 hours in addition to routine
  blood draws needed for treatment of the infants
  illness
• Indwelling catheter exists
• Blood draws will be done through the catheter
• Indwelling catheter does not exist
• 2-3 blood draws occur at clinically indicated
  times
  

7
Clinical Procedures Used

• Tracheal aspirates
• Obtained with routine airway suctioning over the
  next 14 days or as long as infant is intubated
  
• Blood samples
• Drawn before the infusion begins at selected
  intervals over the next 2 weeks
  
• Amount of blood drawn dependent on treatment for
  illness

8
Research Risks

• Rarely blood stream infection
• Isotope infusions are prepared in sterile fashion
  by pharmacists
  
• Rate of blood stream infection to be monitored by
  the Data Monitoring Committee for the study

9
Clinical Risks

• Likely the need for a blood transfusion
• Dependent on the infants illness

10
Benefits

• Develop a better understanding of how surfactant
  is made and used in premature infants
  
• No direct benefits to the infants

11
Expedited Category 2

• Collection of blood samples by finger stick, heel
  stick, ear stick, or venipuncture as follows
  
• from healthy, nonpregnant adults who weigh at
  least 110 pounds. For these subjects, the amounts
  drawn may not exceed 550 ml in an 8 week period
  and collection may not occur more frequently than
  2 times per week
• or
• b) from other adults and children considering
  the age, weight, and health of the subjects, the
  collection procedure, the amount of blood to be
  collected, and the frequency with which it will
  be collected. For these subjects, the amount
  drawn may not exceed the lesser of 50 ml or 3 ml
  per kg in an 8 week period and collection may not
  occur more frequently than 2 times per week.

12
Minimal Risk Collections

• Expedited Category 2
• Does not include or exclude collections through a
  catheter
  
• Specifies 2 times per week for collections
  through finger stick, heel stick, ear stick, or
  venipuncture
  
• Can more collections done if using a catheter?
• Will the study still qualify as minimal risk?

13
45 CFR 46 Risk Classifications

• 46.404 Minimal Risk
• The probability and magnitude of harm or
  discomfort anticipated in the research are not
  greater in and of themselves than those
  ordinarily encountered in daily life or the
  performance of routine physical or psychological
  examinations or tests.
• The study has
• 5 blood draws in a 27 hour period
• Rare risk of bloodstream infections
• Therefore this study does not fit 46.404.

14
45 CFR 46 Risk Classifications

• 46.405 Greater than Minimal and it presents the
  prospect of direct benefit to the participant
  
• The benefits of this study are stated as
• To develop a better understanding of how
  surfactant is made and used in premature infants.
  There is no direct benefit to the participant.
  
• Therefore this study does not fit 46.405.

15
45 CFR 46 Risk Classifications

• 46.406 Greater than minimal with no direct
  benefit to the minors but it is likely to yield
  generalizable knowledge about the subjects
  disorder or condition.
• This study includes control infants in the NICU
  for illnesses not related to lung disease.
  
• The control group does have a disorder or
  condition but the information obtained would not
  yield generalizable knowledge about the control
  groups disorder or condition.
• The control group would not necessarily have
  stable isotopes infused or additional blood draws
  as part of their routine care.
  
• Therefore this study does not fit 46.406.

16
45 CFR 46 Risk Classifications

• 46.407 Uses healthy minors and is greater than
  minimal risk
  
• The study uses
• Infants with normal lungs that are considered
  healthy for this study.
  
• Infusion of isotopes and 5 blood draws in 27
  hours that is considered greater than minimal
  risk.
  

17
Conclusions

• The control group is not really healthy.
• Indirectly, the information obtained could
  provide information on surfactant that would
  eventually benefit any infant that has a
  breathing disorder. But, the committee feels that
  this is not in the spirit of 46.406.
• Therefore, the control group does not really fit
  any category of risk for minors. And, the
  committee concluded that this study should most
  appropriately be classified as 46.407.