Microbiota Restoration Therapy in HIV With Repeated Low-Dose Interventions

NCT03008941 | Completed Phase 1 DMC

• 2 other identifiers: 165-16GESIDA 9116
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HIV Infection

Keywords

HIV; microbiota; inflammation; fecal microbiota restoration

Outcome Measures

Primary Outcomes (1)

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

  From baseline through week 48

Secondary Outcomes (12)

• Changes in CD4+ T cell counts

  From baseline through week 48

• Changes in CD8+ T cell counts

  From baseline through week 48

• Changes in CD4/CD8 ratio

  From baseline through week 48

• Changes in microbiota alpha diversity metrics

  From baseline through week 48

• Changes in microbiota Unifrac distances

  From baseline through week 48

Study Arms (2)

FMT

EXPERIMENTAL

Fecal microbiota capsules (provided by Openbiome). Dosage: * Induction: 10 capsules (single dose) * Maintenance: 5 capsules, weekly, during 7 weeks.

Biological: FMT

Placebo

PLACEBO COMPARATOR

Placebo capsules (provided by Openbiome). Dosage: * Induction: 10 capsules (single dose) * Maintenance: 5 capsules, weekly, during 7 weeks.

Other: Placebo

Interventions

FMT BIOLOGICAL

Capsules with fecal microbiota from healthy donors

FMT

Placebo OTHER

Placebo capsules

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal: lead

Study Sites (1)

Hospital Ramón y Cajal

Madrid, 28034, Spain

Location

Related Publications (1)

• Serrano-Villar S, Talavera-Rodriguez A, Gosalbes MJ, Madrid N, Perez-Molina JA, Elliott RJ, Navia B, Lanza VF, Vallejo A, Osman M, Dronda F, Budree S, Zamora J, Gutierrez C, Manzano M, Vivancos MJ, Ron R, Martinez-Sanz J, Herrera S, Ansa U, Moya A, Moreno S. Fecal microbiota transplantation in HIV: A pilot placebo-controlled study. Nat Commun. 2021 Feb 18;12(1):1139. doi: 10.1038/s41467-021-21472-1.

  PMID: 33602945 DERIVED

MeSH Terms

Conditions

HIV Infections; Inflammation

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: December 28, 2016
• First Posted: January 4, 2017
• Study Start: January 1, 2017
• Primary Completion: June 1, 2018
• Study Completion: October 1, 2018
• Last Updated: October 30, 2018

Record last verified: 2018-10

Locations

ES (1)