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Completed

NCT Number: NCT03008941

Microbiota Restoration Therapy in HIV With Repeated Low-Dose Interventions

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.

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Key information

Conditions

HIV Infection Blood-Borne Infections Communicable Diseases Genital Diseases HIV Infections Immune System Diseases Immunologic Deficiency Syndromes Infections Inflammation Lentivirus Infections Pathologic Processes Pathological Conditions, Signs and Symptoms RNA Virus Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Urogenital Diseases Virus Diseases

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Hospital Ramón y Cajal

Madrid, 28034, Spain

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

FMT

Biological

Capsules with fecal microbiota from healthy donors

Placebo

Other

Placebo capsules

Primary outcomes

  1. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    Time frame: From baseline through week 48

Secondary outcomes

  1. Changes in CD4+ T cell counts

    Time frame: From baseline through week 48

  2. Changes in CD8+ T cell counts

    Time frame: From baseline through week 48

    • Inflammation: interleukin (IL)-6, high sensitivity C reactive protein (hs-CRP), interferon gamma-induced protein (IP)-10.
    • Monocyte/macrophage activation: sCD14, SCD163,
    • Gut epithelial integrity: zonulin-1, intestinal fatty acid binding protein (IFABP).
    • Bacterial translocation: lipoteichoic acid (LTA)
    • Indolamine deoxygenase-1 induction: kynurenine/tryptophan ratio
    • Coagulation: D-dimers

  3. Changes in CD4/CD8 ratio

    Time frame: From baseline through week 48

    • Inflammation: interleukin (IL)-6, high sensitivity C reactive protein (hs-CRP), interferon gamma-induced protein (IP)-10.
    • Monocyte/macrophage activation: sCD14, SCD163,
    • Gut epithelial integrity: zonulin-1, intestinal fatty acid binding protein (IFABP).
    • Bacterial translocation: lipoteichoic acid (LTA)
    • Indolamine deoxygenase-1 induction: kynurenine/tryptophan ratio
    • Coagulation: D-dimers

  4. Changes in microbiota alpha diversity metrics

    Time frame: From baseline through week 48

  5. Changes in microbiota Unifrac distances

    Time frame: From baseline through week 48

  6. Changes in microbiota Canberra distances

    Time frame: From baseline through week 48

  7. Changes in plasma Interleukin-6 levels

    Time frame: From baseline through week 48

  8. Changes in plasma hs-CRP levels

    Time frame: From baseline through week 48

  9. Changes in plasma lipoteichoic acid levels

    Time frame: From baseline through week 48

  10. Changes in plasma LBP levels

    Time frame: From baseline through week 48

  11. Changes in plasma kynurenine/tryptophan ratio

    Time frame: From baseline through week 48

  12. Percentage of HLA-DR+/CD38+ T cells in blood

    Time frame: From baseline through week 48

Sponsors and collaborators

Lead sponsor

Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal

Other

Registry information

Official study 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

Acronym: REFRESH

Important dates

Study start
2017
Primary completion
2018
Study completion
2018
First posted
Jan 4, 2017
Registry last updated
Oct 30, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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