Nutrition, Immunity, and Covid-19 in Obese People (NICO)

Effect of Probiotic and Vitamin D Supplementation in Modulating Gut Dysbiosis, Nutrition, Inflammation and Immune Status and Reduce Risk of COVID-19 in Obese People: Gut-Lung Axis Randomized Trial

The increased risk of transmission of COVID-19 infection causes the incidence of death in health workers to escalate. It requires further research on risk factors and intervention in health worker professionals, especially on immunity factors and nutritional status. Quality of diet and nutrition is very important to support the immune system when infected. Several probiotic strains have been shown to decrease the duration and incidence of diarrhea and respiratory infections, suggesting the Gut-Lung Axis pathway. Some probiotics also improve the balance of diversity in the composition of the gut microbiota and affect body weight in obese people. Probiotics have also been shown to improve vitamin D absorption. A combination of vitamin D and probiotics may be an alternative to reduce gut dysbiosis that will directly or indirectly reduce the risk and severity of viral infections including SARS-CoV-2.

Study Overview

• Status: Recruiting
• Conditions: Covid19; Vitamin D Deficiency; Overweight and Obesity; Immune Deficiency
• Intervention / Treatment: Dietary supplement: Probiotics, Vitamin D; Other: Placebo

Detailed Description

Obesity is increasing in Indonesia and is the cause of various diseases, especially in the presence of Vitamin D deficiency, a state of dysbiosis, causing an increase in the possibility of infection. Professional health workers have a high risk of COVID-19 due to high daily exposure. Based on a review conducted by Daniel et al, it was found that 7.3% of health workers at Reutters University tested positive for COVID-19. Based on data from the Indonesian Doctors Association (IDI) on July 12, 2020, it was known that 61 doctors had died. In addition, based on data from the Indonesian National Nurses Association (PPNI), 39 nurses have died during the COVID-19 pandemic. Therefore efforts to prevent the occurrence of COVID-19 infection by providing a combination of vitamin D and probiotics to modulate dysbiosis that will further reduce the risk of viral infection, especially COVID-19, needs to be investigated for its potential benefits.

Primary and secondary objectives

1. Primary Objective:

   To investigate the effect of a combination of probiotics and vitamin D supplementation in modulating intestinal dysbiosis, and vitamin D status, in people with overweight and obesity, especially among frontline health workers.

   • To assess the mean changes in zonulin levels (as a parameter of gut integrity to indicate the intestinal microbiota dysbiosis)
   • To assess the mean changes in serum vitamin D levels

2. Secondary Objectives:

   • To assess the relationship between nutritional status, inflammation and immunity with the risk of COVID-19 infection in health workers.
   • To understand the difference in the mean episodes of Covid-19 infection between treatment and placebo groups after giving probiotics and vitamin D in people with overweight and obesity, especially among frontline health workers.

Study Design:

This study has 2 phases Phase 1: a Cross-sectional study with 160 people Phase 2: a double-blind, randomized, placebo-controlled trial with two arms of intervention involving a total of 80 people.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rina Agustina, MD, PhD; Phone Number: +62213912477; Email: dr.rinaagustina@gmail.com
• Study Contact Backup: Name: Yani Kurniawan, MD, MM,; Phone Number: +62213912477

Study Locations

• Indonesia
  • DKI Jakarta
    • Jakarta, DKI Jakarta, Indonesia, 10640
      • Recruiting
      • Wisma Emergency COVID-19 Hospital (RSDC)
      • Contact: Tri Widyanti, MSc
    • Jakarta Pusat, DKI Jakarta, Indonesia, 10430
      • Recruiting
      • Department of Nutrition (FKUI-RSCM); and Human Nutrition Research Center, Indonesian Medical Education Research Institute (HNRC-IMERI) Faculty of Medicine, Universitas Indonesia
      • Contact: Rina Agustina; Phone Number: +6221 2912477
      • Contact: Yani Kurniawan; Phone Number: +62213912477; Email: hnrc.imeri@gmail.com
      • Sub-Investigator: Erfi Prafiantini, MSc
      • Sub-Investigator: Yani Kurniawan, MSc
      • Sub-Investigator: Ari Fahrial Syam, Prof
      • Sub-Investigator: Nurul Ratna Mutu Manikam, MSc
      • Sub-Investigator: Davrina Rianda, MSc
      • Sub-Investigator: Hanifa Hanifa, MSc
      • Sub-Investigator: Natasha Dianasari Devana, dr
      • Sub-Investigator: Chaula Putri Rizkia, dr
    • Jakarta Pusat, DKI Jakarta, Indonesia, 10430
      • Recruiting
      • Dr.Cipto Mangunkusumo General Hospital (RSCM)
      • Contact: Unit Bedah Kirana 3rd Floor
  • West Java
    • Depok, West Java, Indonesia, 16424
      • Recruiting
      • University of Indonesia Hospital (RSUI)
      • Contact: Wahyu I Wardhani, Sp.GK(K)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• General doctors, specialist doctors, nurses and midwives who are in charge of handling COVID-19 patients or working in COVID-19 referral hospitals for at least the last 3 months
• 20-65 years old
• Willing to sign informed consent
• Willing to follow the research to completion
• BMI > 23 kg/m2

Exclusion Criteria:

• Pregnant woman
• Have a confirmed history of COVID-19 based on previous PCR examinations
• Suffering from acute illness known from history and physical examination or chronic disease (eg diabetes, SLE, cardiovascular disease) known from history
• Currently not on a diet program for weight loss or consuming probiotics regularly in the last 3 months as known from the anamnesis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Group; Probiotics and Vitamin D	Dietary supplement: Probiotics, Vitamin D; Combination of two supplement that given separately
Placebo Comparator: Control Group; Placebo and placebo	Other: Placebo; Placebo with inactive ingredient

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Zonulin level	To investigate the changes of Zonulin level during intervention	Baseline and endline (3 month)
Vitamin D level	To investigate the changes of Vitamin D level during intervention	Baseline and endline (3 month)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nutritional status	Measurement of nutritional status using Body Mass Index (BMI) and waist circumference	Baseline and endline (3 month)
Gut microbiota (optional)	Measurement of gut microbiota in fecal using Next Generation Sequencing	Baseline and endline (3 month)
Inflammation marker	Measurement of inflammation markers IL-6, IL-10 TNF-α using ELISA	Screening
Cathelicidin level	Measurement of cathelicidin using ELISA	Screening
SARS COV-2	Measurement of quantitative antibody	Screening
CD4/CD8 ratio	Measurement of CD4/CD8 ratio using flowcytometry	Screening
Covid-19 infection	Measurement of the reduction in risk of COVID-19 infection is seen from the difference in the average episodes between groups that were examined by PCR and/or Rapid antibody tests.	Baseline and endline (3 month)

Collaborators and Investigators

• Sponsor: Indonesia University
• Collaborators: Kementerian Riset dan Teknologi / Badan Riset dan Inovasi Nasional, Indonesia
• Investigators: Principal Investigator: Rina Agustina, MD, PhD, HNRC-IMERI, Faculty of Medicine Universitas Indonesia

Publications and helpful links

General Publications

• Zhong NS, Zheng BJ, Li YM, Poon, Xie ZH, Chan KH, Li PH, Tan SY, Chang Q, Xie JP, Liu XQ, Xu J, Li DX, Yuen KY, Peiris, Guan Y. Epidemiology and cause of severe acute respiratory syndrome (SARS) in Guangdong, People's Republic of China, in February, 2003. Lancet. 2003 Oct 25;362(9393):1353-8. doi: 10.1016/s0140-6736(03)14630-2.
• Shereen MA, Khan S, Kazmi A, Bashir N, Siddique R. COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses. J Adv Res. 2020 Mar 16;24:91-98. doi: 10.1016/j.jare.2020.03.005. eCollection 2020 Jul.
• Sattar N, McInnes IB, McMurray JJV. Obesity Is a Risk Factor for Severe COVID-19 Infection: Multiple Potential Mechanisms. Circulation. 2020 Jul 7;142(1):4-6. doi: 10.1161/CIRCULATIONAHA.120.047659. Epub 2020 Apr 22. No abstract available.
• Kass DA, Duggal P, Cingolani O. Obesity could shift severe COVID-19 disease to younger ages. Lancet. 2020 May 16;395(10236):1544-1545. doi: 10.1016/S0140-6736(20)31024-2. Epub 2020 May 4. No abstract available.
• Nagpal R, Newman TM, Wang S, Jain S, Lovato JF, Yadav H. Obesity-Linked Gut Microbiome Dysbiosis Associated with Derangements in Gut Permeability and Intestinal Cellular Homeostasis Independent of Diet. J Diabetes Res. 2018 Sep 3;2018:3462092. doi: 10.1155/2018/3462092. eCollection 2018.
• Calder PC, Carr AC, Gombart AF, Eggersdorfer M. Optimal Nutritional Status for a Well-Functioning Immune System Is an Important Factor to Protect against Viral Infections. Nutrients. 2020 Apr 23;12(4):1181. doi: 10.3390/nu12041181.
• Childs CE, Calder PC, Miles EA. Diet and Immune Function. Nutrients. 2019 Aug 16;11(8):1933. doi: 10.3390/nu11081933.
• Wong SH, Lui RN, Sung JJ. Covid-19 and the digestive system. J Gastroenterol Hepatol. 2020 May;35(5):744-748. doi: 10.1111/jgh.15047. Epub 2020 Apr 19.
• King S, Glanville J, Sanders ME, Fitzgerald A, Varley D. Effectiveness of probiotics on the duration of illness in healthy children and adults who develop common acute respiratory infectious conditions: a systematic review and meta-analysis. Br J Nutr. 2014 Jul 14;112(1):41-54. doi: 10.1017/S0007114514000075. Epub 2014 Apr 29.

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2021
• Primary Completion (Actual): April 30, 2022
• Study Completion (Anticipated): December 30, 2022

Study Registration Dates

• First Submitted: July 24, 2021
• First Submitted That Met QC Criteria: July 24, 2021
• First Posted (Actual): July 27, 2021

Study Record Updates

• Last Update Posted (Actual): August 9, 2022
• Last Update Submitted That Met QC Criteria: August 8, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Vitamin D; Covid-19; Probiotics; Nutrition; Immune status
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Nutrition Disorders; Body Weight; Avitaminosis; Deficiency Diseases; Malnutrition; COVID-19; Vitamin D Deficiency; Overweight; Immunologic Deficiency Syndromes; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Vitamin D
• Other Study ID Numbers: NICO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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