## Protocol Section
### Identification Module
**NCT ID:** NCT01678079

**Acronym:** ENCAP

**Brief Title:** Encapsulated Calcium Absorption in Pregnancy

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

#### Organization Study ID Info
**ID:** 1000033463
#### Organization
**Class:** OTHER
**Full Name:** The Hospital for Sick Children
### Status Module
#### Completion Date
**Date:** 2013-06

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2014-11-18

**Type:** ESTIMATED

**Last Update Submit Date:** 2014-11-17

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2013-06

**Type:** ACTUAL

#### Start Date
**Date:** 2013-02

**Status Verified Date:** 2014-11

#### Study First Post Date
**Date:** 2012-09-03
**Type:** ESTIMATED
**Study First Submit Date:** 2012-08-30
**Study First Submit QC Date:** 2012-08-31
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** International Centre for Diarrhoeal Disease Research, Bangladesh

**Class:** OTHER

**Name:** Baylor College of Medicine

**Class:** OTHER

**Name:** Johns Hopkins Bloomberg School of Public Health

**Class:** UNKNOWN

**Name:** Saving Lives at Birth

**Class:** OTHER

**Name:** Grand Challenges Canada

**Class:** FED

**Name:** United States Agency for International Development (USAID)

**Class:** UNKNOWN

**Name:** Government of Norway

**Class:** OTHER

**Name:** Bill and Melinda Gates Foundation

**Class:** OTHER

**Name:** World Bank

#### Lead Sponsor

**Class:** OTHER

**Name:** The Hospital for Sick Children

#### Responsible Party

**Investigator Affiliation:** The Hospital for Sick Children

**Investigator Full Name:** Daniel Roth

**Investigator Title:** Staff Physician, Paediatric Medicine

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** 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.

### Conditions Module

**Conditions:**

- Pregnancy

**Keywords:**

- Pregnancy

- Micronutrient Powder

- Calcium

- Iron

- Bangladesh

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** CROSSOVER

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 61

**Type:** ACTUAL

**Phases:**

- PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Encapsulated Calcium

**Intervention Names:**

- Dietary Supplement: Encapsulated Calcium

**Label:** Micronutrient Powder, Enteric-coated Calcium (500 mg/day)

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Encapsulated Calcium

**Intervention Names:**

- Dietary Supplement: Encapsulated Calcium

**Label:** Micronutrient Powder, Enteric-coated Calcium (1000 mg/day)

**Type:** EXPERIMENTAL

#### Arm Group 3

**Description:** Encapsulated Calcium

**Intervention Names:**

- Dietary Supplement: Encapsulated Calcium

**Label:** Micronutrient Powder, Enteric-coated Calcium (1500 mg/day)

**Type:** EXPERIMENTAL

#### Arm Group 4

**Description:** Non-capsulated Calcium

**Intervention Names:**

- Dietary Supplement: Non-capsulated Calcium

**Label:** Micronutrient Powder, Uncoated Calcium (500 mg/day)

**Type:** ACTIVE_COMPARATOR

#### Arm Group 5

**Description:** Non-capsulated Calcium

**Intervention Names:**

- Dietary Supplement: Non-capsulated Calcium

**Label:** Micronutrient Powder, Uncoated Calcium (1000 mg/day)

**Type:** ACTIVE_COMPARATOR

#### Arm Group 6

**Description:** Non-capsulated Calcium

**Intervention Names:**

- Dietary Supplement: Non-capsulated Calcium

**Label:** Micronutrient Powder, Uncoated Calcium (1500 mg/day)

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Micronutrient Powder, Enteric-coated Calcium (1000 mg/day)

- Micronutrient Powder, Enteric-coated Calcium (1500 mg/day)

- Micronutrient Powder, Enteric-coated Calcium (500 mg/day)

**Description:** 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).

**Name:** Encapsulated Calcium

**Type:** DIETARY_SUPPLEMENT

#### Intervention 2

**Arm Group Labels:**

- Micronutrient Powder, Uncoated Calcium (1000 mg/day)

- Micronutrient Powder, Uncoated Calcium (1500 mg/day)

- Micronutrient Powder, Uncoated Calcium (500 mg/day)

**Description:** 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.

**Name:** Non-capsulated Calcium

**Type:** DIETARY_SUPPLEMENT

### Outcomes Module

#### Primary Outcomes

**Description:** 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).

**Measure:** Fractional Calcium Absorption

**Time Frame:** Fractional calcium absorption during day 10-11

**Description:** 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).

**Measure:** Fractional Calcium Absorption

**Time Frame:** Fractional calcium absorption during day 35-36

#### Secondary Outcomes

**Description:** 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)

**Measure:** Palatability and Acceptability

**Time Frame:** Baseline, +10/11 days, +35/36 days

### Eligibility Module

**Eligibility Criteria:** 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

**Healthy Volunteers:** True

**Maximum Age:** 30 Years

**Minimum Age:** 18 Years

**Sex:** FEMALE

**Standard Ages:**

- ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Baltimore

**Country:** United States

**Facility:** The Johns Hopkins Bloomberg School of Public Health

**State:** Maryland

**Zip:** 21213

**Location 2:**

**City:** Houston

**Country:** United States

**Facility:** Baylor College of Medicine

**State:** Texas

**Location 3:**

**City:** Dhaka

**Country:** Bangladesh

**Facility:** International Center for Diarrheal Disease Research

**Location 4:**

**City:** Toronto

**Country:** Canada

**Facility:** The Hospital for Sick Children

**State:** Ontario

**Zip:** M5G 1X8

#### Overall Officials

**Official 1:**

**Affiliation:** The Hospital for Sick Children

**Name:** Daniel Roth, MD

**Role:** PRINCIPAL_INVESTIGATOR

**Official 2:**

**Affiliation:** The Hospital for Sick Children

**Name:** Stanley Zlotkin, MD

**Role:** PRINCIPAL_INVESTIGATOR

### References Module

#### References

**Citation:** 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.

**PMID:** 25411294

## Derived Section

### Intervention Browse Module - Ancestors

- ID: D000077264

- Term: Calcium-Regulating Hormones and Agents

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000050071

- Term: Bone Density Conservation Agents

### Intervention Browse Module - Browse Branches

- Abbrev: Micro

- Name: Micronutrients

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Hemat

- Name: Hematinics

- Abbrev: Gast

- Name: Gastrointestinal Agents

- Abbrev: BDCA

- Name: Bone Density Conservation Agents

- Abbrev: Vi

- Name: Vitamins

### Intervention Browse Module - Browse Leaves

- ID: M10533

- Name: Iron

- Relevance: LOW

- As Found: Unknown

- ID: M5381

- Name: Calcium

- Relevance: HIGH

- As Found: Radiation

- ID: M8618

- Name: Folic Acid

- Relevance: LOW

- As Found: Unknown

- ID: M21009

- Name: Micronutrients

- Relevance: LOW

- As Found: Unknown

- ID: M16885

- Name: Trace Elements

- Relevance: LOW

- As Found: Unknown

- ID: M17546

- Name: Vitamin B Complex

- Relevance: LOW

- As Found: Unknown

- ID: M5382

- Name: Calcium Carbonate

- Relevance: LOW

- As Found: Unknown

- ID: M5398

- Name: Calcium, Dietary

- Relevance: HIGH

- As Found: Radiation

- ID: M225448

- Name: Ferrous fumarate

- Relevance: LOW

- As Found: Unknown

- ID: M9789

- Name: Hormones

- Relevance: LOW

- As Found: Unknown

- ID: T447

- Name: Folinic Acid

- Relevance: LOW

- As Found: Unknown

- ID: T446

- Name: Folic Acid

- Relevance: LOW

- As Found: Unknown

- ID: T448

- Name: Folate

- Relevance: LOW

- As Found: Unknown

- ID: T475

- Name: Vitamin B9

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000002136

- Term: Calcium, Dietary

- ID: D000002118

- Term: Calcium

### Misc Info Module

- Version Holder: 2024-05-24
