Vitamin D DeficiencyPhase 2NICONCT04979065
Nutrition, Immunity, and Covid-19 in Obese People
A Phase 2 study testing Probiotics, Vitamin D in people with Vitamin D Deficiency and Covid19, run by Universitas Indonesia at 4 sites in Indonesia.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Vitamin D Deficiency, Covid19, Overweight and Obesity
- What is being tested?
- Probiotics, Vitamin D
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 93 participants
- Where
- 4 sitesIndonesia
- Study dates
- 24 Jul 2021to 30 Dec 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
4 sites in 1 country.
Indonesia4 sites
University of Indonesia Hospital (RSUI)
Depok, West Java, 16424
Wisma Emergency COVID-19 Hospital (RSDC)
Jakarta, DKI Jakarta, 10640
Department of Nutrition (FKUI-RSCM); and Human Nutrition Research Center, Indonesian Medical Education Research Institute (HNRC-IMERI) Faculty of Medicine, Universitas Indonesia
Jakarta Pusat, DKI Jakarta, 10430
Dr.Cipto Mangunkusumo General Hospital (RSCM)
Jakarta Pusat, DKI Jakarta, 10430
About this study
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
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.
Read the 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
- 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
- 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.
- Being tested
- Probiotics, Vitamin D, Placebo
- Keywords
- Probiotics, Vitamin D, Immune status, Covid-19, Nutrition
- Medical subject headings
- Vitamin D Deficiency, COVID-19, Overweight, Obesity, Immunologic Deficiency Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Probiotics, Vitamin DDietary supplement
Combination of two supplement that given separately
PlaceboOther
Placebo with inactive ingredient
| Study group | Role | What they receive |
|---|---|---|
| Experimental Group | Experimental | Probiotics and Vitamin D Receives: Dietary Supplement: Probiotics, Vitamin D |
| Control Group | Placebo comparator | Placebo and placebo Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Zonulin level
To investigate the changes of Zonulin level during intervention
Measured: Baseline and endline (3 month)
Vitamin D level
To investigate the changes of Vitamin D level during intervention
Measured: Baseline and endline (3 month)
Secondary outcomes (7)
Nutritional status
Measurement of nutritional status using Body Mass Index (BMI) and waist circumference
Measured: Baseline and endline (3 month)
Gut microbiota (optional)
Measurement of gut microbiota in fecal using Next Generation Sequencing
Measured: Baseline and endline (3 month)
Inflammation marker
Measurement of inflammation markers IL-6, IL-10 TNF-α using ELISA
Measured: Screening
Cathelicidin level
Measurement of cathelicidin using ELISA
Measured: Screening
SARS COV-2
Measurement of quantitative antibody
Measured: Screening
CD4/CD8 ratio
Measurement of CD4/CD8 ratio using flowcytometry
Measured: 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.
Measured: Baseline and endline (3 month)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2021
- Study start24 Jul 2021
- Primary completion30 Apr 2022
- Study completion30 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Vitamin D DeficiencyStudies of the same condition, open and under way.
- More trials run by Universitas IndonesiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 93 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitas Indonesia
- Sponsor type
- University, hospital or other
- Collaborators
- Kementerian Riset dan Teknologi / Badan Riset dan Inovasi Nasional, Indonesia
- Responsible party
- Principal investigator, Prof Rina Agustina, MD, PhD, Universitas Indonesia
- Investigators
- Rina Agustina, MD, PhD, Principal investigator, HNRC-IMERI, Faculty of Medicine Universitas Indonesia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04979065
- Sponsor's protocol ID
- NICO
- Acronym
- NICO
- Status last verified
- Jun 2024
- First submitted
- 24 Jul 2021
- Last updated
- 4 Jun 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 14585636Shereen 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.
PubMed 32257431Sattar 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.
PubMed 32320270Kass 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.
PubMed 32380044Nagpal 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.
PubMed 30250849Calder 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.
PubMed 32340216Childs CE, Calder PC, Miles EA. Diet and Immune Function. Nutrients. 2019 Aug 16;11(8):1933. doi: 10.3390/nu11081933.
PubMed 31426423Wong 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.
PubMed 32215956King 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.
PubMed 24780623
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04979065
- Acronym / sponsor ID
- NICO / NICO
- Keywords
- Probiotics, Vitamin D, Immune status, Covid-19, Nutrition
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 93 participants (actual)
- Lead sponsor
- Universitas IndonesiaUniversity, hospital or other
- Collaborators
- Kementerian Riset dan Teknologi / Badan Riset dan Inovasi Nasional, Indonesia
- Study start
- 24 Jul 2021 (actual)
- Primary completion
- 30 Apr 2022 (actual)
- Study completion
- 30 Dec 2022 (actual)
- First posted
- 27 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- 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
- 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
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental Group | Experimental | Dietary Supplement: Probiotics, Vitamin DProbiotics and Vitamin D |
| Control Group | Placebo comparator | Other: PlaceboPlacebo and placebo |
Who may qualify
- Ages
- 20 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Probiotics, Vitamin DCombination of two supplement that given separately | Dietary supplement | Experimental Group |
| PlaceboPlacebo with inactive ingredient | Other | Control Group |
Primary outcome
Zonulin level
Time frame: Baseline and endline (3 month)
To investigate the changes of Zonulin level during intervention
Vitamin D level
Time frame: Baseline and endline (3 month)
To investigate the changes of Vitamin D level during intervention
7 secondary outcomes
Nutritional status
Time frame: Baseline and endline (3 month)
Gut microbiota (optional)
Time frame: Baseline and endline (3 month)
Inflammation marker
Time frame: Screening
Cathelicidin level
Time frame: Screening
SARS COV-2
Time frame: Screening
CD4/CD8 ratio
Time frame: Screening
Covid-19 infection
Time frame: Baseline and endline (3 month)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2024.
- Background: PubMed 14585636Zhong 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.
- Background: PubMed 32257431Shereen 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.
- Background: PubMed 32320270Sattar 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.
- Background: PubMed 32380044Kass 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.
- Background: PubMed 30250849Nagpal 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.
- Background: PubMed 32340216Calder 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.
- Background: PubMed 31426423Childs CE, Calder PC, Miles EA. Diet and Immune Function. Nutrients. 2019 Aug 16;11(8):1933. doi: 10.3390/nu11081933.
- Background: PubMed 32215956Wong 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.
- Background: PubMed 24780623King 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rina Agustina, MD, PhD principal investigator
HNRC-IMERI, Faculty of Medicine Universitas Indonesia
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Probiotics, Vitamin D in people with Vitamin D Deficiency and Covid19, run by Universitas Indonesia at 4 sites in Indonesia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Indonesia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Zonulin level (time frame: Baseline and endline (3 month)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04979065, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2024.