Fecal Microbiota Transplantation as a Therapeutic Strategy for Patients Infected With HIV

April 26, 2020 updated by: Dr. Adrian Camacho-Ortiz, Hospital Universitario Dr. Jose E. Gonzalez

Patients eligible for the study will be selected on Fridays during the HIV consultation at the Infectious Diseases Department. Patients that meet the inclusion and exclusion criteria, will be randomized and assigned in two groups 1:1. A group will start intervention with FMT (fecal matter transplant) through frozen capsules and after seven days, antiretroviral therapy (ART) will be started. Patients in the other group will be given placebo capsules and after seven days ART will be started. The frozen capsules of FMT will be ingested orally with a frequency of 15 capsules every 12 hours for 4 doses 7 days prior ART start and on weeks 0, 4, 8 and 12 after ART start. Subsequently, blood samples will be taken to monitor the immune status with CD4 T lymphocytes and HIV viral load during week 0, 4, 8, 12 and 24 after ART start.

Throughout the study period, subjects can carry out a free diet, moderate alcohol intake, perform their daily activities and abstain from any of the elimination criteria. Medical consultations will be made on days -7 to ART start, day 1, 30, 60, 90 and 120 after ART start, where clinical examination and elimination criteria will be evaluated.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Study design: Prospective controlled study experimental comparative Study duration: 1 year The number of patients to enroll: 20 patients. After being randomized, selected patients who meet the criteria for inclusion and exclusion will be assigned 1:1 in two groups. A group will start treatment with FMT through frozen capsules, and ART at the same time; and another group will star placebo capsules and ART.

The frozen capsules will be ingested orally at a frequency of 15 capsules every 12 hours for four doses 7 days prior ART start and on weeks 0, 4, 8 and 12 after ART start. Each capsule must be ingested over a period no longer than 1 hour of the anterior capsule.

Subsequently, blood samples will be taken through peripheral vein puncture with the extraction of 10 ml of venous blood to monitor the immune status with CD4 T lymphocytes and HIV viral load. A total of 4 blood samples will be taken during week 4, 8, 12 and 24 after ART start.

Medical consultations will be made every 4 weeks, on days -7 days prior ART start, day 1, 30, 60, 90 and 120 where vital signs, symptoms or signs of organ systems, determination of weight, BMI, adverse effects and elimination criteria will be assessed.

In addition, feces samples from each patient will be taken during medical consultation on week 0, 8 and 24 after ART start to evaluate the modification of the intestinal microbiome after the intervention on both groups.

During the study period, subjects may carry a free diet, moderate intake of alcohol and perform their daily activities as they refrain free from any of the elimination criteria.

The study will last 1 year and the samples taken will be frozen and stored in the Infectious Diseases Department of the Hospital.

Selection of Fecal Microbiota donors:

The selection of fecal microbiota donors is based on:

  • Medical history, body weight, no medication uses such as antibiotics and proton pump inhibitors, no trips and no diarrhea 6 months prior donation.
  • The absence of chronic infections such as Hepatitis B, Hepatitis C, and HIV determined by immunoassay.
  • Negative Rose Bengal test and V.D.R.L
  • Normal complete blood count and liver function tests.

Fecal sample analysis:

  1. Fresh microscopy analysis to detect leukocytes and parasites (including protozoa and helminths)
  2. Stool culture to rule out the presence of enteropathogens, including Salmonella spp., Shigella spp., Aeromonas spp., Plesiomonas spp., Vibrio spp. and Clostridiodes diffcile.

  3. Gastrointestinal panel by multiple polymerase chain reaction (PCR) using BioFire Filmarray which includes the detection of:

    Bacteria: Campylobacter (C. jejuni, C. coi, C. upsaliensis), Clostridiodes difficile (toxins A / B), Plesiomonas shigelloides, Salmonella spp., Yersinia enterocolitica, Vibrio (V. parahaemolytic , V. vulnificus and V. cholerae), Escherichia coli O157: H7, enteroaggregative E. coli (EAEC), enteropathogenic E. coli (EPEC), enterotoxigenic E. coli (ETEC), Shiga toxin producing E. coli (STEC) stx1 / stx2, Shigella sp. enteroinvasive E. coli (EIEC).

    Virus: Adenovirus F 40/41, Astrovirus, Norovirus GI / GII, Rotavirus A, Sapovirus (I, II, IV and V) Parasites: Cryptosporidium sp., Cyclospora cayetanensis, Entamoeba histolytica and Giardia lamblia.

  4. Detection of genes associated with drug resistance by endpoint PCR; including genes encoding extended spectrum beta-lactamases (TEM, CTX; SHV, CMY) and carbapenemases (VIM, NDM, IMP, KPC, OXA-48).

Once all the stages of evaluation are completed only negative subjects for all the tests and in which there is no evidence of infection are selected as donors. The scrutiny and laboratory tests are considered valid during the following 4 weeks, so if new donation of feces is required, the process will be carried out again.

Sample Preparation fecal microbiota All samples will be mixed with 10% glycerol and frozen at -70°C in a period not exceeding 60 minutes after collection. They will be mixed and then suspended in saline 0.9%. The final mixture will be filtered to remove particles greater than 330 microns, finally adding glycerol as cryoprotectant. This mixture is carried to the encapsulation process using sterile capsules for enteral liberation, in two sizes. The first capsule is filled with a mixture of feces and sealed with its counterpart, and then the sealed capsule becomes encapsulated in a second capsule. The final product is stored frozen until 60 minutes before use. The administration will only be oral.

Study Type

Interventional

Enrollment (Actual)

22

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Mexico
    • Nuevo Leon
      • Monterrey, Nuevo Leon, Mexico, 64460
        • Hospital Universitario José E. Gonzalez

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria:

  • Patients over 18 years
  • Confirmed HIV infection with any CD4 lymphocyte count
  • Patients at the beginning of the study only taking antibiotic prophylaxis according to the CD4 lymphocyte count
  • Patients agree to participate in the study through a signed informed consent

Exclusion criteria:

  • Patients receiving probiotics
  • Patients with anatomical abnormalities of the digestive tract such as colostomy or ileostomy
  • Patients with previous bowel resection
  • Patients with impaired AST and / or ALT greater than 4 times its normal value
  • Hemodialysis patients Patients with gastrointestinal bleeding in the last 12 weeks
  • Patients undergoing colonoscopy in the last 12 weeks

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Patients receiving FMT capsules and ART
  1. ART Start at week 0 non-stop.
  2. FMT. The frozen capsules will be ingested orally at a frequency of 15 capsules every 12 hours for four doses 7 days prior ART start and on weeks 0, 4, 8 and 12 after ART start. Each capsule must be ingested over a period no longer than 1 hour of the anterior capsule.
  3. Blood samples Week 0, 4, 8, 12 and 24. Taken through peripheral vein puncture with the extraction of 10 ml of venous blood to monitor the CD4 lymphocytes count and HIV viral load.
  4. Feces samples from each patient will be taken during medical consultation on week 0, 8 and 24 after ART start to evaluate the modification of the intestinal microbiome.
  5. Medical consultations will be made on days -7 to ART start, day 1, 30, 60, 90 and 120 after ART start, where clinical examination and elimination criteria will be evaluated.
Diagnostic test: Blood and feces samples

Blood samples are going to be taken by puncturing peripheral vein extraction with 10 ml of venous blood for later biweekly to monitor in person and therefore monitor immune status with biomarkers T lymphocyte subclass CD4 and viral load. A total of four blood samples will be taken at weeks 4, 8, 12 and 24 of recruitment.

A total of four feces samples are going to be required during the study, to evaluate the changes on the microbiota of the patient. 1 week before the patients start their HAART, the same day the patients initiate their HAART, 8 weeks after they started HAART and 24 weeks after HAART.
PLACEBO_COMPARATOR: Patients receiving placebo capsules
  1. ART Start at week 0 non-stop.
  2. Placebo capsules. The frozen capsules will be ingested orally at a frequency of 15 capsules every 12 hours for four doses 7 days prior ART start and on weeks 0, 4, 8 and 12 after ART start. Each capsule must be ingested over a period no longer than 1 hour of the anterior capsule.
  3. Blood samples Week 0, 4, 8, 12 and 24. Taken through peripheral vein puncture with the extraction of 10 ml of venous blood to monitor the CD4 lymphocytes count and HIV viral load.
  4. Feces samples from each patient will be taken during medical consultation on week 0, 8 and 24 after ART start to evaluate the modification of the intestinal microbiome.
  5. Medical consultations will be made on days -7 to ART start, day 1, 30, 60, 90 and 120 after ART start, where clinical examination and elimination criteria will be evaluated.
Diagnostic test: Blood and feces samples

Blood samples are going to be taken by puncturing peripheral vein extraction with 10 ml of venous blood for later biweekly to monitor in person and therefore monitor immune status with biomarkers T lymphocyte subclass CD4 and viral load. A total of four blood samples will be taken at weeks 4, 8, 12 and 24 of recruitment.

A total of four feces samples are going to be required during the study, to evaluate the changes on the microbiota of the patient. 1 week before the patients start their HAART, the same day the patients initiate their HAART, 8 weeks after they started HAART and 24 weeks after HAART.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Levels of CD4 cells
Time Frame: 6 months
The efficacy of FMT in obtaining a faster immunologic response measured in rise of CD4 lymphocyte countTMF capsules, will have a faster rise in cell count than those who don´t receive them.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tolerability of FMT capsules
Time Frame: 6 months
Number of Participants with FMT related Adverse Events
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital Universitario Dr. Jose E. Gonzalez

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

September 6, 2018

Primary Completion (ACTUAL)

June 10, 2019

Study Completion (ACTUAL)

January 20, 2020

Study Registration Dates

First Submitted

November 4, 2019

First Submitted That Met QC Criteria

November 13, 2019

First Posted (ACTUAL)

November 15, 2019

Study Record Updates

Last Update Posted (ACTUAL)

April 28, 2020

Last Update Submitted That Met QC Criteria

April 26, 2020

Last Verified

April 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IF18-00008

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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