Determination of Glycine Requirement in Pregnancy

• ClinicalTrials.gov Identifier: NCT02149953
• Recruitment Status: Completed
• First Posted: May 29, 2014
• Last Update Posted: September 23, 2020
• Sponsor: University of British Columbia
• Collaborator: Canadian Institutes of Health Research (CIHR)
• Information provided by (Responsible Party): Rajavel Elango, PhD, University of British Columbia

Tracking Information

• First Submitted Date: May 26, 2014
• First Posted Date: May 29, 2014
• Last Update Posted Date: September 23, 2020
• Actual Study Start Date: September 19, 2014
• Actual Primary Completion Date: September 26, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 28, 2014)

13 Carbon dioxide production [ Time Frame: 8 hours ]

Urine, breath and a single blood sample will be collected during the study to measure the rate of oxidation of tracer in expired breath and flux by enrichment in urine.

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Determination of Glycine Requirement in Pregnancy
• Official Title: Determination Glycine Requirements During Healthy Pregnancy Using the Indicator Amino Acid Oxidation (IAAO) Technique
• Brief Summary: It is important that pregnant women eat an adequate amount of protein to ensure healthy growth and development of the fetus. Amino acids are the building blocks of the body's protein. Glycine is an amino acid that can be made in the body, but under certain metabolic circumstances (e.g. pregnancy) the body's needs may be higher and thus glycine must be obtained from the diet. Currently, it is not known how much glycine may be needed from the diet during pregnancy. We plan to study dietary glycine requirements in healthy pregnant women, during early and late gestation. We will do this using a modern, safe and quick method.

Detailed Description

Purpose:

To determine the dietary glycine requirement in healthy pregnant women during mid (20 - 30 weeks) and late (31 - 40 weeks) gestation.

Hypothesis:

We hypothesize that there is a dietary requirement for glycine during pregnancy due to an increased metabolic demand. With increased glycine intake we hypothesize to observe an increase in protein synthesis, as measured by the indicator amino acid oxidation (IAAO) method.

Justification:

Inadequate protein intake during pregnancy may cause intrauterine growth restriction, which is associated with increased risk of chronic diseases later in life. Currently, the dietary intake recommendations for amino acids are greatly based on nitrogen balance studies of non-pregnant adults. There is little scientific information regarding dietary glycine needs during different stages of pregnancy, despite empirical evidence indicating gestational differences in protein metabolism.

Objectives:

The main objective of the current study is to determine the glycine requirement using the minimally invasive indicator amino acid oxidation (IAAO) method in healthy pregnant women. Our second objective is to compare the glycine requirement during mid (20-30 weeks gestation) and late (31 - 40 weeks gestation) stages of pregnancy.

Research methods:

We will recruit a minimum of 18 pregnant women who may take part in 2 study days in both gestational stages, for a total of 72 study days. Potential participants will meet us for a preliminary assessment where we will evaluate their eligibility to participate in the study. The preliminary study will take approximately 1 hr during which we will examine body composition (bioelectrical impedance, skin-fold measurements, height and weight), resting energy expenditure (indirect calorimetry), blood glucose (glucometer), and medical history (questionnaire). Fasted blood glucose above 6.7 mmol/L is indicative of gestational diabetes. Participants with fasted blood glucose concentrations above 6.7 mmol/L will be referred to follow-up with their primary health care provider (see letter to physician).

We will test the participants urine using a dipstick, to assess whether proteinurea is present. If there is an indication of proteinurea we will refer the participant to their primary physician (See letter to physician - Urine results).

We will collect a 3 day diet record to determine usual food intake and food preferences. Based on the 3 day food record we will prescribe a standardized diet two days prior to the study day to ensure protein intake of 1.5 g/kg/d and energy intake of 1.7 x resting energy.

During each study day, eligible participants will randomly receive 1 of 36 test glycine intakes during both mid and late pregnancy, ranging from 10 to 100 mg/kg/d. Each subject may participate in 2 study days between 20-30 weeks gestation and 2 study days between 31 - 40 weeks gestation, for a total of 4 study days. The test glycine intakes will contain a crystalline L-amino acid mixture based on the composition of egg protein, except for glycine. The test glycine intake will be administered in an experimental diet, along with enough non-protein energy to meet 1.7 x resting energy expenditure of each participant. The diet will be provided as 8 meals, each representing 1/12th of the participant's daily intake requirement. These meals will be provided over the course of an 8 hour study day. A stable isotope tracer will be added to the 5th - 8th meal. We will measure the rate of oxidation of this tracer in expired breath (F13CO2), and flux of this tracer by its enrichment in urine.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Basic Science
• Condition: Pregnancy

Intervention

Dietary Supplement: Glycine Intake

Oral consumption of eight hourly experimental meals- Includes 4 tracer-free experimental meals containing a mixture of free amino acids, calories from a flavored liquid and protein free cookies and 4- labeled amino acid experimental meals.

Study Arms

Experimental: Glycine intake

Dietary supplement: Glycine intake

Intervention: Dietary Supplement: Glycine Intake

• Publications *: Rasmussen BF, Ennis MA, Dyer RA, Lim K, Elango R. Glycine, a Dispensable Amino Acid, Is Conditionally Indispensable in Late Stages of Human Pregnancy. J Nutr. 2021 Feb 1;151(2):361-369. doi: 10.1093/jn/nxaa263.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 22, 2020): 13
• Original Estimated Enrollment (submitted: May 28, 2014): 18
• Actual Study Completion Date: September 26, 2016
• Actual Primary Completion Date: September 26, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Healthy pregnant women aged 20 - 40 yrs
• Singleton pregnancy
• Mid (20 - 30 weeks of gestation) or late stages of pregnancy (31 - 40 weeks of gestation).
• In good health (Free of chronic diseases/acute diseases, full range of physical mobility)

Exclusion Criteria:

• Women who are not pregnant
• Women who are pregnant with more than one child
• Women with history of spontaneous abortion, pre-term birth
• Women who are not in good health or have metabolic, neurologic or immune disorders including; preeclampsia/eclampsia, gestational diabetes, pregnancy-related anemia, pregnancy- related jaundice.
• Women who are substance dependent (i.e. alcohol, cigarette, illicit drugs)
• Women allergic to egg/ egg protein
• Women who have experienced severe nausea and vomiting throughout pregnancy
• Women who are claustrophobic

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 20 Years to 40 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada

Administrative Information

• NCT Number: NCT02149953
• Other Study ID Numbers: H14-00495; F13-04173 ( Other Grant/Funding Number: Canadian Institute of Health Research )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Rajavel Elango, PhD, University of British Columbia
• Original Responsible Party: University of British Columbia
• Current Study Sponsor: University of British Columbia
• Original Study Sponsor: Same as current
• Collaborators: Canadian Institutes of Health Research (CIHR)

Investigators

• Principal Investigator: Rajavel Elango, Ph.D; University of British Columbia

• PRS Account: University of British Columbia
• Verification Date: September 2020