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

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ClinicalTrials.gov Identifier: NCT03568812
Recruitment Status : Recruiting
First Posted : June 25, 2018
Last Update Posted : June 25, 2018
Sponsor:
Information provided by (Responsible Party):
Erni J. Nelwan, Indonesia University

Brief 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.


Condition or disease Intervention/treatment Phase
HIV Infections Immunological Abnormality Drug: Rillus® Other: Placebo Phase 2

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : May 7, 2018
Estimated Primary Completion Date : August 2018
Estimated Study Completion Date : October 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Probiotics 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
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 Name: Rillus® Treatment group

Placebo Comparator: Placebo
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
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.
Other Name: Control group




Primary Outcome Measures :
  1. CD4+ level [ Time Frame: 12 weeks ]
    Change in CD4+ level in blood to assess immune status recovery, measured in cell/μL


Secondary Outcome Measures :
  1. Th17 level [ Time Frame: 12 weeks ]
    Change in Th17 level in blood to assess improvement of gut mucosal integrity and immunity, measured in cell/μL

  2. 16S ribosomal RNA (rRNA) level [ Time Frame: 12 weeks ]
    Change in 16SrRNA of translocated gut bacteria in blood, measured in copies/mL

  3. Fecal calprotectin level [ Time Frame: 12 weeks ]
    Change in calprotectin level in feces to assess gut inflammation, measured in μg/g.

  4. Change in HIV Symptoms Index score [ Time Frame: 0, 4, 8, and 12 weeks ]
    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


Other Outcome Measures:
  1. Change in Food Frequency [ Time Frame: 0,4, 8, 12 weeks ]
    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".



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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03568812


Contacts
Contact: Erni J Nelwan, MD, PhD +62811106563 ejnelwan@yahoo.com

Locations
Indonesia
HIV Clinic, Cipto Mangunkusumo Hospital Recruiting
Jakarta, Indonesia, 10430
Contact: Erni J Nelwan, MD, PhD         
Sponsors and Collaborators
Indonesia University
Investigators
Principal Investigator: Erni J Nelwan, MD, PhD Indonesia University
  Study Documents (Full-Text)

Documents provided by Erni J. Nelwan, Indonesia University:

Responsible Party: Erni J. Nelwan, Principal Investigator, Indonesia University
ClinicalTrials.gov Identifier: NCT03568812     History of Changes
Other Study ID Numbers: 17-10-1001
First Posted: June 25, 2018    Key Record Dates
Last Update Posted: June 25, 2018
Last Verified: June 2018

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

Keywords provided by Erni J. Nelwan, Indonesia University:
HIV
immunological non responder
gut inflammation

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases