HIV InfectionsPhase 2PIONIRNCT03568812
The Role of Probiotics in HIV Patients With Immunological Non-Responder
A Phase 2 study testing Rillus® in people with HIV Infections and Immunological Abnormality, run by Universitas Indonesia at 1 site in Indonesia.
Trial summary
This study will address HIV patients who are on antiretroviral treatment (ART) and experiencing immunological failure. The cause of immunological failure in HIV patients could be due to several factors such as age, gender, Cluster of Differentiation (CD4)+ count before started treatment and some inflammation in the… Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- HIV Infections, Immunological Abnormality
- What is being tested?
- Rillus®
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteIndonesia
- Study dates
- 7 May 2018to 27 Dec 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- HIV patient with immunological non-responder status which defined as:
- first line antiretroviral therapy (ART) treated for minimal 6 months
- CD4+ level between 200-410 cell/μL
- HIV viral load <34 copies/mL
- giving consent to participate the study
Who cannot join
- being pregnant
- lactating
- known Lactobacillus allergy
- BMI <16 kg/m2
- under Tuberculosis treatment or other acute illness
- acute diarrhea
- routinely taking selenium containing vitamin in last 1 month
- routinely consuming probiotics containing product in last 1 month
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Role of Probiotics L. Plantarum, S. Thermophiles, B. Bifidum on Gut Inflammation, Bacterial Translocation, and CD4+ Cell Count in HIV Patients With Immunological Non-Responder
This study will address HIV patients who are on antiretroviral treatment (ART) and experiencing immunological failure. The cause of immunological failure in HIV patients could be due to several factors such as age, gender, Cluster of Differentiation (CD4)+ count before started treatment and some inflammation in the gut. The C-C Chemokine Receptor 5 (CCR5) receptor on T lymphocyte CD4+ are abundantly found in the gut and attacked by HIV virus during acute infection causing irreversible damage.
The disruption of gut integrity and chronic inflammation further causing translocation of bacteria in gut lumen to the blood. Thus resulting persistent low CD4+ or immunological failure.
This evaluation plan is designed to establish the role of investigation product (probiotics) to improve gut inflammation in HIV patients.
Read the detailed description
HIV patients could develop immunological failure despite being treated with antiretroviral therapy (ART). Thus resulting the increase of morbidity and mortality among HIV patients, especially in Indonesia. The immunological failure is associated with decreased gut integrity and immunity, increased gut inflammation, and gut bacterial translocation to the blood. Memory CD4+ T cell damage in gut associated lymphoid tissue (GALT) by HIV-1 virus leads to decreased production of Th17 in gut mucosal layer. Furthermore, low level of Th17 facilitates bacterial translocation in HIV patients.
Probiotic supplementation (Lactobacillus) could decrease the gut inflammation in some diseases including HIV infection; thus helps increasing the gut integrity and immunity by repairing the gut mucosal tight junction, increasing mucin production, and regulating gut Th17. As a result, the gut inflammation and bacterial translocation decreases. Nevertheless, the benefit in HIV patients with immunological non responder status has not been established.
The investigators plan to perform double blind randomized clinical trial of probiotics (containing Lactobacillus plantarum, Streptococcus thermophiles, Bifidobacterium bifidum) in HIV patients with immunological non responder status. The Subject who fulfill inclusion criteria, willing to participate and sign informed consent will be randomized into two groups: the group receiving probiotics (n=40) and the group of placebo (n=40). Intervention will be held for 12 weeks. This study will evaluate the gut mucosal integrity and immunity by Th17 measurement; bacterial translocation by 16S ribosomal RNA (16S RNA) measurement; and gut inflammation by fecal calprotectin measurement before and after the intervention. Moreover, the investigators will measure the CD4+ level to assess immune status recovery before and after the intervention. Side effects, HIV symptom index, Food Frequency Questionnaire will also be assessed every 4 weeks.
Statistical analysis will uses: paired and independent t test (if normally distributed) or using Wilcoxon and Mann Whitney test (if not normally distributed). HIV symptom index and Food frequency will be reported descriptively.
- Conditions
- HIV Infections, Immunological Abnormality
- Being tested
- Rillus®, Placebo
- Keywords
- HIV, immunological non responder, gut inflammation
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rillus®Drug
Also called Rillus® Treatment group
Eligible subjects will be divided into 2 groups randomly (Rillus® or placebo). The colour, smell, flavour, and size of the chewing tablet are the same between active and placebo drugs. Subjects will consume the tablet once daily at night for 12 weeks.
PlaceboOther
Also called Control group
Eligible subjects will be divided into 2 groups randomly (Rillus® or placebo). The colour, smell, flavour, and size of the chewing tablet are the same between active and placebo drugs. Subjects will consume the tablet once daily at night for 12 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Probiotics Rillus® | Experimental | Rillus®, Chewing tablet containing viable cell 1.0 x 10^9 colony forming unit (Lactobacillus plantarum 8.55 mg, Streptococcus thermophilus 8.55 mg, Bifidobacterium bifidum 2.55 mg, fructooligosaccharide 480 mg), isomalt, xylitol, milk flavour, vanilla flavour Dosage: 1 chewing tablet Frequency: once daily every night Duration: 12 weeks Receives: Drug: Rillus® |
| Placebo | Placebo comparator | Placebo: Chewing tablet with identical flavour, colour, smell, and size as investigational drug Dosage: 1 chewing tablet Frequency: once daily every night Duration: 12 weeks Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
CD4+ Level
CD4 level in blood (cell/μL) indicate immune status of patient receiving probiotics or placebo, measure between baseline and at 12 weeks of intervention. Analysis will include CD4 T cell levels after intervention, adjusted with duration of ARV therapy and baseline CD4 levels, as well as unadjusted.
Measured: 12 weeks
Secondary outcomes (4)
Th17 Level Change
Change in Th17 level in blood to assess improvement of gut mucosal integrity and immunity between baseline and at 12 weeks, measured in cell/μL The results was divided in to unadjusted and adjusted Th17 level change.
Measured: 12 weeks
16S Ribosomal RNA (rRNA) Total
Total of 16SrRNA of translocated gut bacteria in blood, measured in copies/mL, presented as median and interquartile range.
Measured: 12 weeks
Fecal Calprotectin Level Change
Change in calprotectin level in feces to assess gut inflammation between baseline and at 12 weeks, measured in μg/g.
The results was divided in to unadjusted and adjusted fecal calprotectin level change
Measured: 12 weeks
Amount of Participants With HIV Related Symptoms
A questionnaire called HIV Symptoms Index (Have been validated in Indonesian language) containing self administered 20 questions consisted of 15 somatic and 5 psychological symptoms to assess Human Immunodeficiency Virus (HIV) related symptoms in patients. The total score is calculated by summing the numbers of each symptom (0 = no symptoms, 1 = no disturbing symptoms, 2 = there are symptoms that are a little annoying, 3 = there are disturbing symptoms, 4 = there are very disturbing symptoms), with a minimum score of 0 and maximum 80. Somatic symptoms range from 0-60 and psychological symptoms range from 0-20. An increase in score indicates a worsening condition. Change in HIV Symptoms Index score to assess improvement of somatic and psychological symptoms between baseline and at 12 weeks.
The results was divided into somatic and psychological symptoms. Both of them were divided again into unadjusted and adjusted HIV Symptoms Index score Change.
Measured: 0,4,8,12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2018
- Study start7 May 2018
- Primary completion27 Dec 2018
- Study completion27 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HIV InfectionsStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- double blind placebo control study
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitas Indonesia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Erni J. Nelwan, Universitas Indonesia
- Investigators
- Erni J Nelwan, MD, PhD, Principal investigator, Universitas Indonesia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03568812
- Sponsor's protocol ID
- 17-10-1001
- Acronym
- PIONIR
- Status last verified
- May 2025
- First submitted
- 14 May 2018
- Last updated
- 4 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Probiotics L. Plantarum, S. Thermophiles, B. Bifidum on Gut Inflammation, Bacterial Translocation, and CD4+ Cell Count in HIV Patients With Immunological Non-Responder
- ClinicalTrials.gov ID
- NCT03568812
- Acronym / sponsor ID
- PIONIR / 17-10-1001
- Conditions
- HIV Infections, Immunological Abnormality
- Keywords
- HIV, immunological non responder, gut inflammation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Universitas IndonesiaUniversity, hospital or other
- Study start
- 7 May 2018 (actual)
- Primary completion
- 27 Dec 2018 (actual)
- Study completion
- 27 Dec 2018 (actual)
- First posted
- 26 Jun 2018 (actual)
- Results
- Posted 4 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will address HIV patients who are on antiretroviral treatment (ART) and experiencing immunological failure. The cause of immunological failure in HIV patients could be due to several factors such as age, gender, Cluster of Differentiation (CD4)+ count before started treatment and some inflammation in the gut. The C-C Chemokine Receptor 5 (CCR5) receptor on T lymphocyte CD4+ are abundantly found in the gut and attacked by HIV virus during acute infection causing irreversible damage.
The disruption of gut integrity and chronic inflammation further causing translocation of bacteria in gut lumen to the blood. Thus resulting persistent low CD4+ or immunological failure.
This evaluation plan is designed to establish the role of investigation product (probiotics) to improve gut inflammation in HIV patients.
Detailed description
HIV patients could develop immunological failure despite being treated with antiretroviral therapy (ART). Thus resulting the increase of morbidity and mortality among HIV patients, especially in Indonesia. The immunological failure is associated with decreased gut integrity and immunity, increased gut inflammation, and gut bacterial translocation to the blood. Memory CD4+ T cell damage in gut associated lymphoid tissue (GALT) by HIV-1 virus leads to decreased production of Th17 in gut mucosal layer. Furthermore, low level of Th17 facilitates bacterial translocation in HIV patients.
Probiotic supplementation (Lactobacillus) could decrease the gut inflammation in some diseases including HIV infection; thus helps increasing the gut integrity and immunity by repairing the gut mucosal tight junction, increasing mucin production, and regulating gut Th17. As a result, the gut inflammation and bacterial translocation decreases. Nevertheless, the benefit in HIV patients with immunological non responder status has not been established.
The investigators plan to perform double blind randomized clinical trial of probiotics (containing Lactobacillus plantarum, Streptococcus thermophiles, Bifidobacterium bifidum) in HIV patients with immunological non responder status. The Subject who fulfill inclusion criteria, willing to participate and sign informed consent will be randomized into two groups: the group receiving probiotics (n=40) and the group of placebo (n=40). Intervention will be held for 12 weeks. This study will evaluate the gut mucosal integrity and immunity by Th17 measurement; bacterial translocation by 16S ribosomal RNA (16S RNA) measurement; and gut inflammation by fecal calprotectin measurement before and after the intervention. Moreover, the investigators will measure the CD4+ level to assess immune status recovery before and after the intervention. Side effects, HIV symptom index, Food Frequency Questionnaire will also be assessed every 4 weeks.
Statistical analysis will uses: paired and independent t test (if normally distributed) or using Wilcoxon and Mann Whitney test (if not normally distributed). HIV symptom index and Food frequency will be reported descriptively.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- double blind placebo control study
| Arm | Type | Receives |
|---|---|---|
| Probiotics Rillus® | Experimental | Drug: Rillus®Rillus®, Chewing tablet containing viable cell 1.0 x 10^9 colony forming unit (Lactobacillus plantarum 8.55 mg, Streptococcus thermophilus 8.55 mg, Bifidobacterium bifidum 2.55 mg, fructooligosaccharide 480 mg), isomalt, xylitol, milk flavour, vanilla flavour Dosage: 1 chewing tablet Frequency: once daily every night Duration: 12 weeks |
| Placebo | Placebo comparator | Other: PlaceboPlacebo: Chewing tablet with identical flavour, colour, smell, and size as investigational drug Dosage: 1 chewing tablet Frequency: once daily every night Duration: 12 weeks |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- HIV patient with immunological non-responder status which defined as:
- first line antiretroviral therapy (ART) treated for minimal 6 months
- CD4+ level between 200-410 cell/μL
- HIV viral load <34 copies/mL
- giving consent to participate the study
Key exclusion criteria (8 listed)
- being pregnant
- lactating
- known Lactobacillus allergy
- BMI <16 kg/m2
- under Tuberculosis treatment or other acute illness
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 |
|---|---|---|
| Rillus®Also: Rillus® Treatment groupEligible subjects will be divided into 2 groups randomly (Rillus® or placebo). The colour, smell, flavour, and size of the chewing tablet are the same between active and placebo drugs. Subjects will consume the tablet once daily at night for 12 weeks. | Drug | Probiotics Rillus® |
| PlaceboAlso: Control groupEligible subjects will be divided into 2 groups randomly (Rillus® or placebo). The colour, smell, flavour, and size of the chewing tablet are the same between active and placebo drugs. Subjects will consume the tablet once daily at night for 12 weeks. | Other | Placebo |
Primary outcome
CD4+ Level
Time frame: 12 weeks
CD4 level in blood (cell/μL) indicate immune status of patient receiving probiotics or placebo, measure between baseline and at 12 weeks of intervention. Analysis will include CD4 T cell levels after intervention, adjusted with duration of ARV therapy and baseline CD4 levels, as well as unadjusted.
4 secondary outcomes
Th17 Level Change
Time frame: 12 weeks
16S Ribosomal RNA (rRNA) Total
Time frame: 12 weeks
Fecal Calprotectin Level Change
Time frame: 12 weeks
Amount of Participants With HIV Related Symptoms
Time frame: 0,4,8,12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Erni J Nelwan, MD, PhD principal investigator
Universitas Indonesia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rillus® in people with HIV Infections and Immunological Abnormality, run by Universitas Indonesia at 1 site 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 8 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 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Yes. Results are posted in the registry (first posted 4 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
CD4+ Level (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 May 2025.