Oral Sucrose Versus Glucose for Procedural Pain in Premature Neonates

NCT ID: NCT01894659

Last Updated: 2020-09-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 51 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-02-28
• Study Completion Date: 2020-07-31

Brief Summary

Premature neonates admitted to the neonatal intensive care unit (NICU) require up to several hundred procedures during their hospitalization. Many of these are tissue-damaging procedures (TDPs) that cause pain. Through our NIH funded research, we made the novel observation that exposure to a single TDP can significantly increase ATP utilization and oxidative stress, as evidenced by increased plasma levels of hypoxanthine, uric acid and malondialdehyde in neonates exposed to TDPs as compared to controls (no TDP). Because neonates are exposed to numerous TDPs, it is relevant to explore the energy costs of repeated exposures to painful procedures, an important information that is currently not known, as the effect of this cumulative metabolic dysfunction could result in potentially treatable or preventable cell injury.

Oral sucrose analgesia is frequently given to relieve procedural pain in neonates on the basis of its effect on behavioral and physiological pain scores. However, we found, through our prospective, randomized, double blind study funded by NIH, that although oral sucrose significantly reduced pain scores, its administration before a single TDP (heel lance) significantly increased ATP utilization. This is evidenced by higher plasma concentrations of hypoxanthine and uric acid in neonates given sucrose compared to control neonates (no TDP, no sucrose) or neonates just given a pacifier. These novel findings raise concern because preterm neonates have limited ATP stores and are susceptible to cell injury due to ATP depletion. In addition, it raises the relevant concern: If a single dose of oral sucrose can alter ATP metabolism, what are the effects of exposure to multiple doses of oral sucrose? More importantly, what is the effect of multiple TDPs and/or multiple oral sucrose dosages on ATP utilization, oxidative stress and cell injury? This application will also explore the effect of 30% oral glucose, another sweet solution currently used to relieve pain, on ATP metabolism.

In this study, we will test the general hypothesis that exposure to multiple TDPs and/or multiple doses of oral sucrose analgesia compared to oral glucose or standard care, alter biochemical markers of ATP utilization, oxidative stress and cell injury. We will use a prospective randomized clinical research design to test this hypothesis during days of life 3-7 of human premature neonates. Increased ATP utilization will be quantified by concentrations of hypoxanthine, xanthine and uric acid measured using HPLC. Oxidative stress will be quantified by concentrations of allantoin using gas chromatography/mass spectroscopy, and cell injury will be quantified through urinary concentration of intestinal fatty acid binding protein, an early marker of enterocyte injury. Data from this application will provide insight into the cellular and biochemical effects of repetitive and accumulated TDPs and/or multiple doses of oral sucrose. With this knowledge, we will propose and test innovative strategies that will not only decrease pain but also will prevent cell injury or cell death.

Conditions

Neonatal Procedural Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: QUADRUPLE

Study Groups

Control

Neonates randomized to this arm will receive the standard of practice at Loma Linda University NICU.

Group Type: NO_INTERVENTION

No interventions assigned to this group

24% oral sucrose with pacifier

Neonates randomized to this arm will receive 24% sucrose before every painful procedure on days of life 3-7 in the NICU.

Group Type: EXPERIMENTAL

24% oral sucrose

Intervention Type: OTHER

30% oral glucose with pacifier

Neonates randomized to this arm will receive 30% oral glucose before every painful procedure on days of life 3-7.

Group Type: EXPERIMENTAL

30% oral glucose

Intervention Type: OTHER

Interventions

24% oral sucrose

Intervention Type: OTHER

30% oral glucose

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Potential subjects are premature infants ≤ 34 weeks gestation and ≤ 7 days of age postnatally

Exclusion Criteria

1. requirement for surgery

2. intraventricular hemorrhage (IVH) ≥ grade 3

3. neonates on medications such as morphine, fentanyl, versed, muscle relaxants, phenobarbital, or dilantin,

4. renal injury (plasma creatinine > 1 mg/dl,

5. severe cyanotic heart disease or severe respiratory distress,

6. known abdominal wall or intestinal anomaly or injury (NEC),

7. chromosomal anomaly and (8) facial anomaly

• Maximum Eligible Age: 7 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Loma Linda University

OTHER

Sponsor Role: lead

Responsible Party

Danilyn Angeles, PhD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Danilyn Angeles, PhD

Role: PRINCIPAL_INVESTIGATOR

Loma Linda University

Locations

Loma Linda University Medical Center

Loma Linda, California, United States

Countries

United States

Other Identifiers

5130117

Identifier Type: -

Identifier Source: org_study_id