Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03568812
Recruitment Status : Completed
First Posted : June 26, 2018
Last Update Posted : July 1, 2019
Sponsor:
Information provided by (Responsible Party):
Erni J. Nelwan, Indonesia University

Tracking Information
First Submitted Date  ICMJE May 14, 2018
First Posted Date  ICMJE June 26, 2018
Last Update Posted Date July 1, 2019
Actual Study Start Date  ICMJE May 7, 2018
Actual Primary Completion Date December 27, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 22, 2018)
CD4+ level [ Time Frame: 12 weeks ]
Change in CD4+ level in blood to assess immune status recovery, measured in cell/μL
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 22, 2018)
  • 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
  • 16S ribosomal RNA (rRNA) level [ Time Frame: 12 weeks ]
    Change in 16SrRNA of translocated gut bacteria in blood, measured in copies/mL
  • Fecal calprotectin level [ Time Frame: 12 weeks ]
    Change in calprotectin level in feces to assess gut inflammation, measured in μg/g.
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: June 22, 2018)
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".
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE The Role of Probiotics in HIV Patients With Immunological Non-Responder
Official Title  ICMJE 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
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.

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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
double blind placebo control study
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • HIV Infections
  • Immunological Abnormality
Intervention  ICMJE
  • 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
  • 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
Study Arms  ICMJE
  • 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
    Intervention: Drug: Rillus®
  • 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
    Intervention: Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 22, 2018)
80
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 27, 2018
Actual Primary Completion Date December 27, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Indonesia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03568812
Other Study ID Numbers  ICMJE 17-10-1001
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Erni J. Nelwan, Indonesia University
Study Sponsor  ICMJE Indonesia University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Erni J Nelwan, MD, PhD Indonesia University
PRS Account Indonesia University
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP