We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    microbiota transplant HIV | Recruiting Studies
Previous Study | Return to List | Next Study

Microbiota Restoration Therapy in HIV With Repeated Low-Dose Interventions (REFRESH)

This study is currently recruiting participants.
Verified January 2017 by Sergio Serrano-Villar, Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
Sponsor:
ClinicalTrials.gov Identifier:
NCT03008941
First Posted: January 4, 2017
Last Update Posted: January 18, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Sergio Serrano-Villar, Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
  Purpose
Altered interplay between gut mucosa and dysbiotic bacteria during HIV infection seems to contribute to chronic immune dysfunction. Manipulation of the intestinal microbiota with nutritional interventions exert limited immunologic effects, but a deep understanding of how these interventions could ameliorate gut dysbiosis and influence health among HIV-infected individuals remain unexplored. In this Phase I clinical trial, 30 HIV-infected subjects on effective ART with evidence of persistent immune dysfunction, indicated by a CD4/CD8 ratio<1 will be included and randomized to either repeated low-dose oral fecal microbiota transplantation or placebo during 8 weeks. The primary outcome will be safety. Secondary outcomes will include changes in CD4+ T cell counts, CD8+ T cell counts, CD4/CD8 ratio, inflammatory markers, T cell activation and markers of enterocyte barrier function through week 48. Engraftment on host microbiota will be examined using Illumina sequencing of the V3-V4 16S RNA, and changes in bacterial metabolism and in the plasma metabolite fingerprint will be studied by combination of untargeted mass spectrometry and two different and complementary separation techniques in bacterial and plasma samples.

Condition Intervention Phase
HIV Infection Biological: FMT Other: Placebo Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase I/II Randomized, Double-Blind, Placebo Controlled Study of Repeated Low-Dose Fecal Microbiota Restoration in HIV-Infected Subjects. The REFRESH Study

Resource links provided by NLM:


Further study details as provided by Sergio Serrano-Villar, Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal:

Primary Outcome Measures:
  • Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: From baseline through week 48 ]

Secondary Outcome Measures:
  • Changes in CD4+ T cell counts [ Time Frame: From baseline through week 48 ]
  • Changes in CD8+ T cell counts [ Time Frame: From baseline through week 48 ]
    1. Inflammation: interleukin (IL)-6, high sensitivity C reactive protein (hs-CRP), interferon gamma-induced protein (IP)-10.
    2. Monocyte/macrophage activation: sCD14, SCD163,
    3. Gut epithelial integrity: zonulin-1, intestinal fatty acid binding protein (IFABP).
    4. Bacterial translocation: lipoteichoic acid (LTA)
    5. Indolamine deoxygenase-1 induction: kynurenine/tryptophan ratio
    6. Coagulation: D-dimers

  • Changes in CD4/CD8 ratio [ Time Frame: From baseline through week 48 ]
    1. Inflammation: interleukin (IL)-6, high sensitivity C reactive protein (hs-CRP), interferon gamma-induced protein (IP)-10.
    2. Monocyte/macrophage activation: sCD14, SCD163,
    3. Gut epithelial integrity: zonulin-1, intestinal fatty acid binding protein (IFABP).
    4. Bacterial translocation: lipoteichoic acid (LTA)
    5. Indolamine deoxygenase-1 induction: kynurenine/tryptophan ratio
    6. Coagulation: D-dimers

  • Changes in microbiota alpha diversity metrics [ Time Frame: From baseline through week 48 ]
  • Changes in microbiota Unifrac distances [ Time Frame: From baseline through week 48 ]
  • Changes in microbiota Canberra distances [ Time Frame: From baseline through week 48 ]
  • Changes in plasma Interleukin-6 levels [ Time Frame: From baseline through week 48 ]
  • Changes in plasma hs-CRP levels [ Time Frame: From baseline through week 48 ]
  • Changes in plasma lipoteichoic acid levels [ Time Frame: From baseline through week 48 ]
  • Changes in plasma LBP levels [ Time Frame: From baseline through week 48 ]
  • Changes in plasma kynurenine/tryptophan ratio [ Time Frame: From baseline through week 48 ]
  • Percentage of HLA-DR+/CD38+ T cells in blood [ Time Frame: From baseline through week 48 ]

Estimated Enrollment: 30
Study Start Date: January 2017
Estimated Study Completion Date: February 2019
Estimated Primary Completion Date: October 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: FMT

Fecal microbiota capsules (provided by Openbiome).

Dosage:

  • Induction: 10 capsules (single dose)
  • Maintenance: 5 capsules, weekly, during 7 weeks.
Biological: FMT
Capsules with fecal microbiota from healthy donors
Placebo Comparator: Placebo

Placebo capsules (provided by Openbiome).

Dosage:

  • Induction: 10 capsules (single dose)
  • Maintenance: 5 capsules, weekly, during 7 weeks.
Other: Placebo
Placebo capsules

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • On stable antiretroviral therapy with plasma HIV RNA <20 copies/mL during at least 48 weeks.
  • CD4/CD8 ratio <1

Exclusion Criteria:

  • Pregnancy
  • Gastrointestinal diseases, including cirrhosis
  • Active infections, including HCV
  • EBV and/or CMV negative patients (donors are not screened for EBV/CMV).
  • Planned used of chemotherapy or antibiotics
  • Allergy to sodium chloride or glycerol (the former components are capsule ingredients Generally Recognized As Safe (GRAS)
  • Current or planned use of antimicrobial agents (including prophylactic treatments against P. jiroveci) other than ART.
  • Neutropenia <500 cells/uL or CD4 counts <350 cells/uL
  • Patients unable to give informed consent
  • Patients unable to comply with the protocol requirements
  • Predicted death within time period of follow-up
  • Any other condition for which the treating physician thinks the treatment may pose a health risk
  • Dysphagia: oropharyngeal, esophageal, functional, neuromuscular (e.g. stroke, multiple sclerosis, ALS)
  • History of aspiration
  • History of gastroparesis
  Contacts and Locations
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): NCT03008941


Contacts
Contact: Itziar Abechuco ceic.hrc@salud.madrid.org

Locations
Spain
Hospital Ramón y Cajal Recruiting
Madrid, Spain, 28034
Contact: Sergio Serrano-Villar, MD; PhD       sergio.serrano@salud.madrid.org   
Sponsors and Collaborators
Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
  More Information

Responsible Party: Sergio Serrano-Villar, MD, PhD, Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
ClinicalTrials.gov Identifier: NCT03008941     History of Changes
Other Study ID Numbers: 165-16
GESIDA 9116 ( Other Identifier: GESIDA Study group )
First Submitted: December 28, 2016
First Posted: January 4, 2017
Last Update Posted: January 18, 2017
Last Verified: January 2017

Keywords provided by Sergio Serrano-Villar, Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal:
HIV
microbiota
inflammation
fecal microbiota restoration

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