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

• ClinicalTrials.gov Identifier: NCT04979065
• Recruitment Status: Recruiting
• First Posted: July 27, 2021
• Last Update Posted: August 9, 2022
• Sponsor: Indonesia University
• Collaborator: Kementerian Riset dan Teknologi / Badan Riset dan Inovasi Nasional, Indonesia
• Information provided by (Responsible Party): Rina Agustina, Indonesia University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Vitamin D Deficiency; Covid19; Overweight and Obesity; Immune Deficiency	Dietary Supplement: Probiotics, Vitamin D; Other: Placebo	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Independent party will mask the product
• Primary Purpose: Prevention
• Official Title: 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
• Actual Study Start Date: July 24, 2021
• Actual Primary Completion Date: April 30, 2022
• Estimated Study Completion Date: December 30, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Zonulin level [ Time Frame: Baseline and endline (3 month) ]
   To investigate the changes of Zonulin level during intervention
2. Vitamin D level [ Time Frame: Baseline and endline (3 month) ]
   To investigate the changes of Vitamin D level during intervention

Secondary Outcome Measures :

1. Nutritional status [ Time Frame: Baseline and endline (3 month) ]
   Measurement of nutritional status using Body Mass Index (BMI) and waist circumference
2. Gut microbiota (optional) [ Time Frame: Baseline and endline (3 month) ]
   Measurement of gut microbiota in fecal using Next Generation Sequencing
3. Inflammation marker [ Time Frame: Screening ]
   Measurement of inflammation markers IL-6, IL-10 TNF-α using ELISA
4. Cathelicidin level [ Time Frame: Screening ]
   Measurement of cathelicidin using ELISA
5. SARS COV-2 [ Time Frame: Screening ]
   Measurement of quantitative antibody
6. CD4/CD8 ratio [ Time Frame: Screening ]
   Measurement of CD4/CD8 ratio using flowcytometry
7. Covid-19 infection [ Time Frame: Baseline and endline (3 month) ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Contacts

Contact: Rina Agustina, MD, PhD; +62213912477; dr.rinaagustina@gmail.com

Contact: Yani Kurniawan, MD, MM,; +62213912477

Locations

Indonesia

Department of Nutrition (FKUI-RSCM); and Human Nutrition Research Center, Indonesian Medical Education Research Institute (HNRC-IMERI) Faculty of Medicine, Universitas Indonesia; Recruiting

Jakarta Pusat, DKI Jakarta, Indonesia, 10430

Contact: Rina Agustina +6221 2912477

Contact: Yani Kurniawan +62213912477 hnrc.imeri@gmail.com

Principal Investigator: Rina Agustina, PhD

Sub-Investigator: Erfi Prafiantini, MSc

Sub-Investigator: Yani Kurniawan, MSc

Sub-Investigator: Ari Fahrial Syam, Prof

Sub-Investigator: Murdani Abdullah, 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

Dr.Cipto Mangunkusumo General Hospital (RSCM); Recruiting

Jakarta Pusat, DKI Jakarta, Indonesia, 10430

Contact: Unit Bedah Kirana 3rd Floor

Wisma Emergency COVID-19 Hospital (RSDC); Recruiting

Jakarta, DKI Jakarta, Indonesia, 10640

Contact: Tri Widyanti, MSc

University of Indonesia Hospital (RSUI); Recruiting

Depok, West Java, Indonesia, 16424

Contact: Wahyu I Wardhani, Sp.GK(K)

Sponsors and Collaborators

Indonesia University

Kementerian Riset dan Teknologi / Badan Riset dan Inovasi Nasional, Indonesia

Investigators

• Principal Investigator: Rina Agustina, MD, PhD; HNRC-IMERI, Faculty of Medicine Universitas Indonesia

More Information

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.

• Responsible Party: Rina Agustina, Head of Human Nutrition Research Centre / Principal Investigator, Indonesia University
• ClinicalTrials.gov Identifier: NCT04979065
• Other Study ID Numbers: NICO
• First Posted: July 27, 2021
• Last Update Posted: August 9, 2022
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Rina Agustina, Indonesia University:

Probiotics; Vitamin D; Immune status; Covid-19; Nutrition

Additional relevant MeSH terms:

COVID-19; Vitamin D Deficiency; Immunologic Deficiency Syndromes; Overweight; Respiratory Tract Infections; Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Body Weight; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Immune System Diseases; Vitamin D; Vitamins; Micronutrients; Physiological Effects of Drugs; Bone Density Conservation Agents