Encapsulated Calcium Absorption in Pregnancy (ENCAP)

Bioavailability and Acceptability of Enteric-Coated Microencapsulated Calcium During Pregnancy: A Randomized Crossover Trial in Bangladesh (Encapsulated Calcium Absorption in Pregnancy)

This study will enroll at least 60 pregnant women in a randomized cross-over study in Dhaka, Bangladesh. Each participant will be randomized to one of 3 calcium doses: 500 mg, 1000 mg, 1500 mg elemental Ca per day. Each participant will undergo two calcium absorption tests, one with a micronutrient supplement powder containing non-encapsulated (non-coated) calcium and the other with a micronutrient supplement powder containing encapsulated calcium at the same dose. The absorption tests will be separated by a 2-week washout period. Fractional calcium absorption will be measured using the dual stable isotope method. For each test, the formulation will be administered orally for 9 days; on the 10th day, a 44Ca- labeled stable isotope will be given orally and a 42Ca-labeled stable isotope dose will be given intravenously. Urine will be collected for 48 hours to measure calcium absorption.

Study Overview

• Status: Completed
• Conditions: Pregnancy
• Intervention / Treatment: Dietary supplement: Encapsulated Calcium; Dietary supplement: Non-capsulated Calcium

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 1

Contacts and Locations

Study Locations

• Bangladesh
  • Dhaka, Bangladesh
    • International Center for Diarrheal Disease Research
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children
• United States
  • Maryland
    • Baltimore, Maryland, United States, 21213
      • The Johns Hopkins Bloomberg School of Public Health
  • Texas
    • Houston, Texas, United States
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Women aged 18 to 30 years
• Current residence in Dhaka at a fixed address
• Plan to remain in Dhaka for at least 2 months from date of enrolment
• Gestational age of 27 completed weeks ± 1 week, estimated based on the recalled first day of the last menstrual period (LMP)

Exclusion Criteria:

• Complicated medical or obstetric history, based on self-report or clinical assessment by physician (e.g., cardiovascular disease, uterine hemorrhage, placenta previa, threatened abortion, hypertension, preeclampsia, multiple gestation, diabetes, renal disease)

• Higher risk pregnancy based on one or more of the following clinical findings at time of recruitment:

  • Severe anemia (hemoglobin <70 g/L assessed by Hemocue)
  • Proteinuria (≥ 100 mg/dl based on urine dipstick)
  • Glycosuria (≥ 100 mg/dl based on urine dipstick)
  • Hypertension (systolic blood pressure, ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg)
• Reported use of dietary supplements that contain >500 mg of calcium per day and/or >400 IU (10 mcg) of vitamin D per day
• Reported use (chewing) of betel leaf, areca nut and lime (together referred to locally as paan) during pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Micronutrient Powder, Enteric-coated Calcium (500 mg/day); Encapsulated Calcium	Dietary supplement: Encapsulated Calcium; The intervention is a multi-micronutrient powder containing enteric-coated calcium carbonate, in addition to ferrous fumarate (60 mg of elemental iron) and folic acid (400 µg).
Experimental: Micronutrient Powder, Enteric-coated Calcium (1000 mg/day); Encapsulated Calcium	Dietary supplement: Encapsulated Calcium; The intervention is a multi-micronutrient powder containing enteric-coated calcium carbonate, in addition to ferrous fumarate (60 mg of elemental iron) and folic acid (400 µg).
Experimental: Micronutrient Powder, Enteric-coated Calcium (1500 mg/day); Encapsulated Calcium	Dietary supplement: Encapsulated Calcium; The intervention is a multi-micronutrient powder containing enteric-coated calcium carbonate, in addition to ferrous fumarate (60 mg of elemental iron) and folic acid (400 µg).
Active Comparator: Micronutrient Powder, Uncoated Calcium (500 mg/day); Non-capsulated Calcium	Dietary supplement: Non-capsulated Calcium; The comparator/control intervention is a micronutrient powder containing non-coated calcium (500, 1000 or 1500 mg elemental calcium from calcium carbonate), ferrous fumarate (60 mg of elemental iron) and folic acid (400 µg). This product will be similar in Ca dose, appearance, taste and texture to the experimental formulation but will not include the enteric-coating.
Active Comparator: Micronutrient Powder, Uncoated Calcium (1000 mg/day); Non-capsulated Calcium	Dietary supplement: Non-capsulated Calcium; The comparator/control intervention is a micronutrient powder containing non-coated calcium (500, 1000 or 1500 mg elemental calcium from calcium carbonate), ferrous fumarate (60 mg of elemental iron) and folic acid (400 µg). This product will be similar in Ca dose, appearance, taste and texture to the experimental formulation but will not include the enteric-coating.
Active Comparator: Micronutrient Powder, Uncoated Calcium (1500 mg/day); Non-capsulated Calcium	Dietary supplement: Non-capsulated Calcium; The comparator/control intervention is a micronutrient powder containing non-coated calcium (500, 1000 or 1500 mg elemental calcium from calcium carbonate), ferrous fumarate (60 mg of elemental iron) and folic acid (400 µg). This product will be similar in Ca dose, appearance, taste and texture to the experimental formulation but will not include the enteric-coating.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fractional Calcium Absorption	The primary analysis will be a comparison of mean fractional absorption of the two calcium formulations (enteric-coated vs. non-coated). The secondary analysis will be a comparison of mean fractional absorption across different calcium doses (500, 1000, 1500 mg per day).	Fractional calcium absorption during day 10-11
Fractional Calcium Absorption	The primary analysis will be a comparison of mean fractional absorption of the two calcium formulations (enteric-coated vs. non-coated). The secondary analysis will be a comparison of mean fractional absorption across different calcium doses (500, 1000, 1500 mg per day).	Fractional calcium absorption during day 35-36

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Palatability and Acceptability	The palatability and acceptability of the microencapsulated and non-encapsulated calcium formulations will be surveyed to assess the following parameters using semi-quantitative measures (i.e. Organoleptic properties, such as taste, odour, texture and colour, and adherence to prescribed micronutrient regimen, and reasons for non-adherence)	Baseline, +10/11 days, +35/36 days

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children
• Collaborators: Baylor College of Medicine; Johns Hopkins Bloomberg School of Public Health; United States Agency for International Development (USAID); Bill and Melinda Gates Foundation; International Centre for Diarrhoeal Disease Research, Bangladesh; Grand Challenges Canada; World Bank; Saving Lives at Birth; Government of Norway
• Investigators: Principal Investigator: Daniel Roth, MD, The Hospital for Sick Children; Principal Investigator: Stanley Zlotkin, MD, The Hospital for Sick Children

Publications and helpful links

General Publications

• Roth DE, Pezzack B, Al Mahmud A, Abrams SA, Islam M, Aimone Phillips A, Baxter JA, Dimitris MC, Hawthorne KM, Ahmed T, Zlotkin SH. Bioavailability of enteric-coated microencapsulated calcium during pregnancy: a randomized crossover trial in Bangladesh. Am J Clin Nutr. 2014 Dec;100(6):1587-95. doi: 10.3945/ajcn.114.090621. Epub 2014 Oct 1.

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: August 30, 2012
• First Submitted That Met QC Criteria: August 31, 2012
• First Posted (Estimate): September 3, 2012

Study Record Updates

• Last Update Posted (Estimate): November 18, 2014
• Last Update Submitted That Met QC Criteria: November 17, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: Pregnancy; Iron; Bangladesh; Calcium; Micronutrient Powder
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Calcium; Calcium, Dietary
• Other Study ID Numbers: 1000033463

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No