The Role of Probiotics in HIV Patients With Immunological Non-Responder

HIV Infections Clinical Trial

— PIONIR  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03568812
• Other study ID #: 17-10-1001
• Status: Completed
• Phase: Phase 2
• Start date: May 7, 2018
• Est. completion date: December 27, 2018

Study information

• Verified date: June 2019
• Source: Indonesia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: December 27, 2018
• Est. primary completion date: December 27, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• HIV Infections
• Immunological Abnormality

Intervention

Drug:
• Rillus®
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.

Other:
• Placebo
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.

Locations

Country	Name	City	State
Indonesia	HIV Clinic, Cipto Mangunkusumo Hospital	Jakarta

Sponsors (1)

Lead Sponsor	Collaborator
Indonesia University

Country where clinical trial is conducted

Indonesia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Food Frequency	A questionnaire consisted of food and drink list and frequency to assess patients' dietary pattern in the past one week. Nutritionist will be asking the participants for the questionnaire questions. The food frequency scaled to "more than one time daily", "once daily", "3-6 times in one week", "1-2 times in one week", "less than one time in one week", "never".	0,4, 8, 12 weeks
Primary	CD4+ level	Change in CD4+ level in blood to assess immune status recovery, measured in cell/µL	12 weeks
Secondary	Th17 level	Change in Th17 level in blood to assess improvement of gut mucosal integrity and immunity, measured in cell/µL	12 weeks
Secondary	16S ribosomal RNA (rRNA) level	Change in 16SrRNA of translocated gut bacteria in blood, measured in copies/mL	12 weeks
Secondary	Fecal calprotectin level	Change in calprotectin level in feces to assess gut inflammation, measured in µg/g.	12 weeks
Secondary	Change in HIV Symptoms Index score	A questionnaire containing 20 questions to assess HIV related symptoms in patients. Self administered. Each item is scored 0-4 (0= not experiencing the symptom; 4 = severely disturbing). The result will be presented descriptively	0, 4, 8, and 12 weeks