Efficacy and Safety of Low-dose Calcium Supplementation in Pregnancy

NCT07784218 | Completed Phase 4 DMC

• 1 other identifier: CARE Pilot
• Study Type: interventional
• Target: 117
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a prospective, randomized, double-blind controlled pilot trial designed to comprehensively evaluate the efficacy and safety of a targeted low-dose (300 mg/day) versus a standard high-dose (600 mg/day) calcium supplementation during mid-to-late pregnancy. The main research content is divided into the following four core dimensions:

1. 1.Evaluation of Maternal Skeletal and Systemic Calcium Efficacy: The core efficacy evaluation focuses on the preservation of maternal bone mineral density throughout mid-to-late pregnancy. This is assessed by the change in the BMD Z-score (ΔZ-score) from baseline to delivery using quantitative ultrasound (QUS). Concurrently, by comparing pre- and post-intervention maternal serum total calcium concentrations, the study verifies whether the low-dose regimen is sufficient to maintain normal systemic calcium homeostasis and support fetal development.
2. 2.Safety Assessment of Renal Filtration and Metabolic Burden: To investigate the potential metabolic toxicity of high-dose calcium, the study explicitly evaluates the maternal renal calcium excretion burden. By measuring the change in the fasting urinary calcium-to-creatinine ratio (ΔU-Ca/Cr) before and after the intervention, the research aims to determine whether the targeted low-dose regimen effectively prevents iatrogenic absorptive hypercalciuria induced by excessive calcium overload.
3. 3.Evaluation of Clinical Gastrointestinal Tolerability: Given that gastrointestinal adverse events are the primary deterrent to prenatal supplement adherence, this study utilizes the internationally recognized Rome IV criteria to rigorously track and compare the time-to-onset and cumulative incidence of moderate-to-severe constipation between the two groups, thereby quantifying the difference in intestinal tolerability between the dosages.
4. 4.Exploration of Adverse Pregnancy Outcomes and General Safety: As an exploratory clinical endpoint, the study records and compares the incidence rates of preeclampsia and preterm birth between the two intervention arms to ensure the low-dose regimen safely maintains prophylactic benefits against adverse obstetric outcomes. Furthermore, a comprehensive panel of maternal general laboratory parameters (e.g., hepatic and renal function, lipid profiles, and hematology) is monitored throughout to guarantee overall systemic safety.

Conditions

Pregnancy

Keywords

Pregnancy; Calcium Supplementation

Outcome Measures

Primary Outcomes (2)

• ΔZ-score

  Change in Bone Mineral Density (BMD) Z-score from baseline to delivery measured by Quantitative Ultrasound (QUS)

  Baseline and before delivery

• Moderate-to severe constipation

  Time-to-onset and cumulative incidence of moderate-to-severe constipation (Rome IV criteria)

  Through study completion, an average of 20 weeks

Secondary Outcomes (2)

• Serum calcium

  Baseline and before delivery

• ΔU-Ca/Cr

  Baseline and before delivery

Other Outcomes (1)

• Cumulative incidences of preeclampsia and preterm birth

  Through study completion, an average of 20 weeks

Study Arms (2)

Treatment

EXPERIMENTAL

Calcium supplementation 300 mg/day

Drug: Calcium

Control

ACTIVE COMPARATOR

Calcium supplementation 600 mg/day

Drug: Calcium

Interventions

Calcium DRUG

Participants in the treatment group received calcium 300 mg/day and the control group received calcium 600 mg/day.

Control; Treatment

Eligibility Criteria

• Age: 14 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Pregnant women aged 18 to 45 years
• Gestational age between 22 and 28 weeks
• Body mass index (BMI) between 19.0\~28.0 kg/m2
• Willingness to comply with the study protocol and provision of informed consent

You may not qualify if:

• Known hypersensitivity or allergy to any active components or excipients of the study medications
• Multifetal gestation
• History of chronic constipation or functional defecation disorders prior to or during early pregnancy
• Current clinical hypercalcemia, hyperuricemia, familial hyperlipidemia, or intestinal malabsorption disorders
• History of prolonged extreme low-calcium diets or severe diagnosed nutritional deficiencies
• History of illicit substance abuse, chronic alcoholism, heavy smoking, or excessive caffeine intake

Sponsors & Collaborators

• First People's Hospital of Hangzhou: lead

Study Sites (1)

Hangzhou First People's Hospital

Hangzhou, China

Location

MeSH Terms

Interventions

Calcium

Intervention Hierarchy (Ancestors)

Metals, Alkaline Earth; Elements; Inorganic Chemicals; Metals; Blood Coagulation Factors; Biological Factors

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Attending Physician

Study Record Dates

• First Submitted: August 17, 2026
• First Posted: August 25, 2026
• Study Start: September 10, 2025
• Primary Completion: May 20, 2026
• Study Completion: July 8, 2026
• Last Updated: August 25, 2026

Record last verified: 2026-08

Locations

CN (1)