Zinc and Copper Absorption in Neonates With Bilious Losses

This study has been completed.
Sponsor:
Information provided by:
Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT00738283
First received: August 18, 2008
Last updated: December 9, 2010
Last verified: December 2010
  Purpose

We propose to examine the absorption and excretion of zinc and copper in infants with ostomies. This will be accomplished by measuring baseline excretion and serum levels of zinc, copper, and ceruloplasmin, and by utilizing stable isotopes of zinc and copper to measure absorption and excretion.

To determine how the presence of an ileostomy impacts zinc and copper metabolism in infants at three time points: 1) when the infant has an ostomy and is receiving the majority of calories from total parenteral nutrition (TPN); 2) when the infant has an ostomy and is receiving primarily enteral nutrition without TPN; and 3) when/if the infant has a surgery to reconnect the bowel and is receiving primarily enteral nutrition.

For the first part of the study, excretion data for zinc will be obtained for ostomy patients. We hypothesize that infants with an ostomy will excrete more zinc in their stools than healthy term or preterm infants without ostomies.

For the second part of the study, we will obtain data on zinc absorption, secretion, and excretion through use of stable isotopes. Jalla et al determined that healthy infants retain zinc of 0.4 mg/day. We hypothesize that due to increased zinc losses, the infants in the study will be less positive than the healthy infants in the study by Jalla et al. Our study is designed to be able to detect if the ostomy patients net retention is one-half that described by Jalla (i.e. 0.2 mg/d). We will also obtain data on copper absorption, secretion, and excretion through the use of stable isotopes in the second part of the study. As a pilot study, we do not fully know what to expect regarding copper levels in infants with ostomies, but we hypothesize that they may be less positive than healthy infants without ostomies. Also, we hypothesize that zinc and copper are competitively absorbed in the gut; therefore, infants who receive more zinc may absorb less copper.

For the third part of the study, we will obtain data on zinc absorption through the use of stable isotopes after the infant has had surgery to reanastomose the bowel. We hypothesize that there may be continued zinc losses above those documented for healthy infants who have never had an ostomy, but decreased losses compared to when the infant had an ostomy.


Condition
Ileostomy

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Zinc and Copper Absorption in Neonates With Bilious Losses

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • The primary objective of this study revolves around part 2, the stable isotope portion of zinc and copper absorption, secretion, and excretion in infants with an ostomy. There is currently no data available in this population for zinc balance. [ Time Frame: Assessed at the end of the study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Additional objectives that will be accomplished by the study include establishment of baseline secretion of zinc while on TPN in part one of the study, and determination of the effect of reanastomosis on zinc secretion in the third part of the study. [ Time Frame: Assessed at the end of the study ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples Without DNA

Blood, stool, gastric residuals, and urine


Estimated Enrollment: 20
Study Start Date: September 2008
Study Completion Date: December 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
  Hide Detailed Description

Detailed Description:

Potential subjects will be identified by study personnel in the Neonatal Intensive Care Units (NICU) of Texas Children's Hospital and Ben Taub General Hospital. The parent/guardian will be approached and the study will be explained in full. A time for questions will be allowed. Once the parent/guardian agrees to his/her child's participation, an informed written consent form will be signed. Subject confidentiality will be maintained within the limits of the law. All names and personal information will be accessed only by the investigators and authorized personnel. There will be no possibility of coercion as subjects will not have any relationship of dependency with the investigators.

We intend to asses zinc and copper metabolism at three time points: first, when the infant has an ostomy and is receiving primarily intravenous nutrition, called total parenteral nutrition (TPN), with minimal or no enteral feeds (ie, feeds into the gastrointestinal tract); second, when the infant has an ostomy and is receiving primarily enteral nutrition without TPN; and third, when/if the infant has a surgery to reconnect the bowel and remove the ostomy. Using stable isotope techniques for the second and third parts, we will measure intake compared to excretions (stool in ostomy and urine). A stable isotope is naturally occurring form of a mineral that we can measure, or trace, in the body. It is not radioactive and there are no known risks from it.

Part 1: This part will not include any stable isotopes. We will collect the ostomy and urine output for 24 hours to determine the zinc and copper content of the ostomy output and the urine. A small collection of blood (2 mL) will also be obtained at the same time other routine blood tests are being done. This blood will be tested for zinc, copper, and ceruloplasmin levels. If the infant has a replogle or other gastric tube, gastric residuals will be collected during the same 24 hours that stool from the ostomy is collected. If for some reason Part 1 is not able to be performed before the subject meets the criteria for Part 2, the subject will not be dropped. Part 1 will be considered optional. The following will be measured: zinc intake (from the zinc content of the TPN), endogenous fecal excretion (from the ostomy and gastric outputs) and urinary zinc excretion (from the urine collection). Zinc balance will be estimated from the difference in zinc intake and zinc output (in the ostomy, urine, and gastric fluid). Copper balance will be measured from the difference in copper intake (in TPN) and copper losses (in the ostomy, urine and gastric fluid).

Part 2: The second part of the study will occur when the infant has reached full enteral feedings (minimum of 100 cc/kg/day) and TPN has been discontinued. This part of the study will include stable isotopes. Infants should be receiving a steady state volume and concentration of feedings per kg for at least two (2) days and throughout the first 24 hours of the sample collection period. The time recorded that the infant receives the first isotope will mark the beginning of the sample collection period. Infants may be receiving either breast milk (fortified or unfortified) or infant formula. If the infant is receiving breast milk, a 10mL sample of breast milk will be obtained to determine zinc and copper content. Zinc and copper contents of infant formula will be determined from published tables by the manufacturer. The infant will receive 1 mg Zn67 and 80 mcg Cu65 stable isotope orally mixed into one of the infant's morning feedings on the study day. In addition, the infant will receive 0.1 mg Zn70 intravenous stable isotope. Stool will be collected from the ostomy bag for 72 hours. A urine bag will be placed on the infant's skin to collect all the urine for 24 hours, followed by a spot urine sample collection twice a day for three (3) days after the isotope infusion. The final urine collection should occur at approximately 96 hours after the isotope infusion. A small amount of blood (2 mL) will also be taken at the time of the intravenous isotope infusion. This blood will be tested for zinc, copper, and ceruloplasmin levels. Fractional zinc absorption and endogenous fecal zinc excretion will be measured using stable isotopes. Urinary excretion will be measured from the urine collection. Zinc balance will be calculated from the difference in absorbed zinc (intake x fractional absorption) and zinc losses (urinary excretion and endogenous fecal zinc excretion). Fractional copper absorption will be measured from the difference in intake of Cu65 and the losses of Cu65 (in the ostomy and urine). Copper balance will be measured from the difference in total copper intake and total copper losses (in the ostomy and urine).

Part 3: The third part of the study will occur after the infant has a surgery to reconnect the bowel and remove the ostomy. A spot urine sample will be obtained prior to the stable isotope infusion to ensure that isotope previously consumed/infused will not be considered in the data analysis for this part of the study. The stable isotope study will occur whenever the infant's bowel has been reconnected and the infant has achieved a steady volume and concentration of feedings per kg (minimum of 100 cc/kg/day) for at least 2 days. This volume will continue throughout the first 24 hours of the sample collection period. Infants may be receiving either breast milk (fortified or unfortified) or infant formula. If the infant is receiving breast milk, a 10mL sample of breast milk will be obtained to determine zinc and copper content. Zinc and copper contents of infant formula will be determined from published tables by the manufacturer.

As the ostomy bag has been removed, it will be difficult to obtain stool samples for 72 hours. Therefore, we will only measure zinc urine excretion, not secretion and will not be able to assess copper balance at this time point. The infant will receive 1 mg Zn67 orally mixed into one of the infant's morning feedings on the study day. In addition, the infant will receive 0.1 mg Zn70 intravenously. A small collection of blood (2 mL) will also be taken at the time of the isotope infusion. This blood will be tested for zinc, copper, and ceruloplasmin levels. One spot urine sample will be obtained at 96 hours after the first isotope is received.

Study-related information will be recorded from the medical record and will include type and volume of enteral feedings, volume and concentrations of TPN, anthropometrics, nutrition-related lab results from routine blood draws (ie, BUN, creatinine, electrolytes, bilirubin, calcium, phosphorus, alkaline phosphatase, and triglycerides), and ostomy and urine output.

Recognizing that there is the possibility that not every infant will have a surgery to reconnect the bowel, the consent form will clearly state that their child may or may not be eligible for Part 3.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Subjects will be selected from the patient population at the Neonatal Intensive Care Units of Texas Children's Hospital and Ben Taub General Hospital.

Criteria

Inclusion Criteria:

  • Presence of ileostomy due to any disease or condition (i.e., necrotizing enterocolitis, intestinal atresias, gastroschisis, or intestinal perforations)
  • Minimum birth weight of 500g
  • Likely to survive

Exclusion Criteria:

  • Dysmotility of the gastrointestinal system
  • Major congenital anomalies, including heart disease
  • Meconium ileus
  • Not expected to survive for at least 2 weeks
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00738283

Locations
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
Texas Children's Hospital
Houston, Texas, United States, 77030
Ben Taub General Hospital
Houston, Texas, United States, 77030
Sponsors and Collaborators
Baylor College of Medicine
Investigators
Principal Investigator: Steven A Abrams, MD Baylor College of Medicine
  More Information

Additional Information:
Publications:
Responsible Party: Steve Abrams, MD, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT00738283     History of Changes
Other Study ID Numbers: H-23224
Study First Received: August 18, 2008
Last Updated: December 9, 2010
Health Authority: United States: Institutional Review Board

Keywords provided by Baylor College of Medicine:
Zinc
Copper
Neonate

Additional relevant MeSH terms:
Copper
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 20, 2014