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

Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal

Status and phase

Completed

Phase 2

Phase 1

Conditions

HIV Infection

Treatments

Other: Placebo

Biological: FMT

Study type

Interventional

Funder types

Other

Identifiers

NCT03008941

165-16

GESIDA 9116 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment

30 patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

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