Calcium-vitamin D & Periodontal Therapy for Improving Metabolic and Inflammatory Profile Among Pregnant Women (IMPROVE)

Calcium and Vitamin D Supplementation and Periodontal Therapy for Improving Metabolic and Inflammatory Profile Among Pregnant Women: a Feasibility Trial (THE IMPROVE TRIAL)

The improvement of maternal and child health remains a key issue in global health. Production and improved accessibility of healthy and nutrient-rich milk-based products could potentially tackle health and nutrition inequalities in low-income countries.

This study will assess the acceptability of a multi-component intervention, including provision of calcium/vitamin-D fortified milk and periodontal therapy (PT), for improving maternal periodontal health and metabolic and inflammatory profiles. The IMPROVE trial is a feasibility randomised controlled trial (RCT) with parallel qualitative process evaluation. The target population is low-income, pregnant, Brazilian women, with periodontitis, who have not seen a dentist in the last 6 months. A series of focus group discussions and interviews with the target population will be conducted to identify key barriers and enablers to adoption and implementation of the intervention in prenatal clinics in Rio de Janeiro/Brazil. Participants will be allocated to 4 groups: 1) early PT (during pregnancy) plus fortified milk; 2) early PT plus plain milk; 3) delayed PT (after delivery) plus fortified milk; 4) delayed PT plus plain milk.

The final results will contribute to the understanding of the significance of calcium and vitamin D for short and long-term health and the occurrence of diseases, as well as to inform the current global debate on vitamin-D supplementation and fortification policy.

Study Overview

• Status: Completed
• Conditions: Inflammation; Periodontitis
• Intervention / Treatment: Other: Early PT; Dietary supplement: Fortified Milk; Dietary supplement: Plain Milk; Other: Delayed PT

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • Rio de Janeiro, Brazil
    • Centro Municipal de Saúde de Duque de Caxias & Policlínica Hospital Duque de Caxias

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 49 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Aged ≥ 18 year;
• Up to 16 weeks' gestation;
• Having ≥ 20 teeth;
• Diagnosis of periodontitis (≥ 1 tooth with at least one of periodontal sites with ≥ 4 mm of clinical attachment loss and bleeding on probing on the same site);
• Not received regular dental treatment in the last 6 months (except from those who only visited the dentist for an emergency appointment e.g. tooth extraction);
• Cognitively and physically able to complete an interview and oral examination; and
• Willing to participate (including provision of blood samples)

Exclusion Criteria:

• Diagnosis of HIV/AIDS, psychosis, diabetes before pregnancy, thyroid disease, or disorders causing vitamin D hypersensitivity (e.g. sarcoidosis and other lymphomatous disorders);
• Diagnosis of lactose intolerance or milk allergy;
• History of renal stones or family history of renal stone and hyperparathyroidism;
• presence of extensive dental cavity and decay;
• Use of antibiotics or any immune-suppressants or medication known to affect vitamin D/calcium metabolism; and
• Consumption of ≥4 servings/day of dairy products or taking vitamin D supplements at > 400 IU/day.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early PT plus Fortified Milk; early periodontal therapy (during pregnancy) plus fortified milk	Other: Early PT; Women will receive conventional non-surgical periodontal therapy (PT), consisting of prophylactic dental polishing to remove the sticky bacterial film that forms on the teeth over time, scaling and root planing, as necessary throughout pregnancy, up to delivery; Other Names: Early non-surgical periodontal therapy; Dietary supplement: Fortified Milk; participants will be advised to take two servings of a powdered milk-based drink enriched with calcium and vitamin D daily during breakfast and afternoon snack or supper to avoid concomitant intake of the prenatal iron supplements routinely prescribed for consumption with hot main meals (e.g. lunch or dinner). Women will be advised to consume 20 g of commercially available semi-skimmed milk powder (provided by the study) and one sachet with 500 IU of vitamin D3 and 1,2 g of a calcium supplement from milk extract (300 mg of calcium) twice a day.
Experimental: Early PT plus Plain Milk; early periodontal therapy (during pregnancy) plus plain milk	Other: Early PT; Women will receive conventional non-surgical periodontal therapy (PT), consisting of prophylactic dental polishing to remove the sticky bacterial film that forms on the teeth over time, scaling and root planing, as necessary throughout pregnancy, up to delivery; Other Names: Early non-surgical periodontal therapy; Dietary supplement: Plain Milk; Women will be advised to consume 20 g of commercially available semi-skimmed milk powder (provided by the study) and one sachet with flour (placebo).; Other Names: non-fortified milk (placebo)
Experimental: Delayed PT plus Fortified Milk; delayed periodontal therapy (after delivery) plus fortified milk	Dietary supplement: Fortified Milk; participants will be advised to take two servings of a powdered milk-based drink enriched with calcium and vitamin D daily during breakfast and afternoon snack or supper to avoid concomitant intake of the prenatal iron supplements routinely prescribed for consumption with hot main meals (e.g. lunch or dinner). Women will be advised to consume 20 g of commercially available semi-skimmed milk powder (provided by the study) and one sachet with 500 IU of vitamin D3 and 1,2 g of a calcium supplement from milk extract (300 mg of calcium) twice a day.; Other: Delayed PT; Women will receive conventional non-surgical PT delayed until after delivery.; Other Names: Delayed non-surgical periodontal therapy
Placebo Comparator: Delayed PT plus Plain Milk; delayed periodontal therapy (after delivery) plus plain milk	Dietary supplement: Plain Milk; Women will be advised to consume 20 g of commercially available semi-skimmed milk powder (provided by the study) and one sachet with flour (placebo).; Other Names: non-fortified milk (placebo); Other: Delayed PT; Women will receive conventional non-surgical PT delayed until after delivery.; Other Names: Delayed non-surgical periodontal therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility (acceptability of study design, recruitment strategy, random allocation and data collection procedures)	Feasibility will be evaluated using mixed-methods to explore intervention delivery, participants' acceptability, challenges and issues faced during the study, and recommended changes to the study design. Focus groups discussions will be held prior to trial recruitment to discuss issues regarding recruitment strategy, study design and data collection. In addition, group discussions will be held throughout the study (2nd and 3rd trimester) to assess potential barriers and facilitators to the intervention and data collection. At the end of each participant's involvement in the study, the participant will be asked to complete an anonymous, acceptability questionnaire to gain insights about participant's reactions to research participation and how acceptable the participant found study requirements and assessments were.	From baseline till 6-8 weeks' postpartum
Recruitment rate	This will be measured by the total number of participants recruited into the study. The investigators intend to recruit 120 participants. Recruitment rate will be calculated (number of participants per month)	one year
Adherence	number of drop-outs in each study arm. Analyses of drop-out rates (%) in four study arms. Self-reported quantity of milk consumed during the study. Number of follow-up visits. Proportion of participants who provide full data at baseline, throughout pregnancy and up to 6-8 weeks postpartum.	From baseline till 6-8 weeks' postpartum

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in % of sites with bleeding on probing	Certified and calibrated dentists will conduct dental examinations pre/post-intervention. Full mouth periodontal examination will be performed at six sites per tooth, using disposable periodontal probes with coloured-coded area and mirror but without X-rays. Bleeding scores will be determined as percentage of sites with bleeding relative to the total number of sites examined.	baseline and 6-8 weeks' postpartum
Changes in maternal blood biomarkers to assess inflammation	Blood samples will be taken to assess changes in cytokines levels: CRP, IL-6 and MMP-9.	10 months on average
Changes in maternal serum levels of 25(OH)D	Blood samples will be taken to assess changes in 25(OH)D levels	10 months on average
Changes in maternal glucose levels	Fasting blood samples will be taken to assess changes in glucose levels	10 months on
Changes in maternal insulin levels	Fasting blood samples will be taken to assess changes in insulin levels	10 months on average
Changes in maternal serum levels of calcium	Fasting blood samples will be taken to assess changes in calcium levels	10 months on average
Changes in maternal blood lipids levels	Fasting blood samples will be taken to assess changes in total cholesterol and HDL-c	10 months on average
Neonatal levels of 25(OH)D	drops of neonatal capillary blood will be collected via heel prick (200 μl) for measurement of 25(OH)D concentrations at the routine neonatal check-up	between 8 to 22 months
Neonatal levels of calcium	drops of neonatal capillary blood will be collected via heel prick (200 μl) for measurement of calcium concentrations	between 8 to 22 months

Collaborators and Investigators

• Sponsor: University of Westminster
• Collaborators: Boston University; University of Oxford; Rio de Janeiro State University; Copenhagen University Hospital, Denmark; Universidade Federal do Rio de Janeiro; Instituto Fernandes Figueira

Publications and helpful links

General Publications

• Rodrigues Amorim Adegboye A, Cocate PG, Benaim C, da Veiga Soares Carvalho MC, Schlussel MM, de Castro MBT, Kac G, Heitmann BL. Recruitment of low-income pregnant women into a dietary and dental care intervention: lessons from a feasibility trial. Trials. 2020 Mar 5;21(1):244. doi: 10.1186/s13063-020-4142-5.
• Cocate PG, Kac G, Heitmann BL, Nadanovsky P, da Veiga Soares Carvalho MC, Benaim C, Schlussel MM, de Castro MBT, Alves-Santos NH, Baptista AF, Holick MF, Mokhtar RR, Bomfim AR, Adegboye ARA. Calcium and vitamin D supplementation and/or periodontal therapy in the treatment of periodontitis among Brazilian pregnant women: protocol of a feasibility randomised controlled trial (the IMPROVE trial). Pilot Feasibility Stud. 2019 Mar 5;5:38. doi: 10.1186/s40814-019-0417-6. eCollection 2019. Erratum In: Pilot Feasibility Stud. 2020 Nov 27;6(1):187.

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2017
• Primary Completion (Actual): May 30, 2018
• Study Completion (Actual): May 30, 2018

Study Registration Dates

• First Submitted: October 27, 2016
• First Submitted That Met QC Criteria: May 8, 2017
• First Posted (Actual): May 11, 2017

Study Record Updates

• Last Update Posted (Actual): August 3, 2021
• Last Update Submitted That Met QC Criteria: July 27, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Feasibility; Periodontitis; Pregnant women; Periodontal Therapy; Pregnancy outcome; Milk Fortification
• Additional Relevant MeSH Terms: Pathologic Processes; Stomatognathic Diseases; Periodontal Diseases; Mouth Diseases; Periodontitis; Inflammation
• Other Study ID Numbers: 2602

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: External users will be bound by a data sharing agreement (in Portuguese and English) which will be available as part of the application to share data on the University website

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No