HIV InfectionPhase 1/2REFRESHNCT03008941
Microbiota Restoration Therapy in HIV With Repeated Low-Dose Interventions
A Phase 1/2 study testing FMT in people with HIV Infection, run by Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal at 1 site in Spain.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- HIV Infection
- What is being tested?
- FMT
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteSpain
- Study dates
- Jan 2017to Oct 2018
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- On stable antiretroviral therapy with plasma HIV RNA <20 copies/mL during at least 48 weeks.
- CD4/CD8 ratio <1
Who cannot join
- 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)
Show all 15Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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
- Being tested
- FMT, Placebo
- Keywords
- HIV, microbiota, inflammation, fecal microbiota restoration
- Medical subject headings
- HIV Infections, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FMTBiological
Capsules with fecal microbiota from healthy donors
PlaceboOther
Placebo capsules
| Study group | Role | What they receive |
|---|---|---|
| FMT | Experimental | Fecal microbiota capsules (provided by Openbiome).
Dosage:
* Induction: 10 capsules (single dose)
* Maintenance: 5 capsules, weekly, during 7 weeks. Receives: Biological: FMT |
| Placebo | Placebo comparator | Placebo capsules (provided by Openbiome).
Dosage:
* Induction: 10 capsules (single dose)
* Maintenance: 5 capsules, weekly, during 7 weeks. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Measured: From baseline through week 48
Secondary outcomes (12)
Changes in CD4+ T cell counts
Measured: From baseline through week 48
Changes in CD8+ T cell counts
- 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
Measured: From baseline through week 48
Changes in CD4/CD8 ratio
- 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
Measured: From baseline through week 48
Changes in microbiota alpha diversity metrics
Measured: From baseline through week 48
Changes in microbiota Unifrac distances
Measured: From baseline through week 48
Changes in microbiota Canberra distances
Measured: From baseline through week 48
Changes in plasma Interleukin-6 levels
Measured: From baseline through week 48
Changes in plasma hs-CRP levels
Measured: From baseline through week 48
Changes in plasma lipoteichoic acid levels
Measured: From baseline through week 48
Changes in plasma LBP levels
Measured: From baseline through week 48
Changes in plasma kynurenine/tryptophan ratio
Measured: From baseline through week 48
Percentage of HLA-DR+/CD38+ T cells in blood
Measured: From baseline through week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jan 2017 (estimated)
- Study startJan 2017
- Primary completionJun 2018
- Study completionOct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sergio Serrano-Villar, Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03008941
- Sponsor's protocol ID
- 165-16
- Other IDs
- GESIDA 9116
- Acronym
- REFRESH
- Status last verified
- Oct 2018
- First submitted
- 28 Dec 2016
- Last updated
- 30 Oct 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 33602945
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03008941
- Acronym / sponsor ID
- REFRESH / 165-16
- Conditions
- HIV Infection
- Keywords
- HIV, microbiota, inflammation, fecal microbiota restoration
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y CajalUniversity, hospital or other
- Study start
- Jan 2017 (actual)
- Primary completion
- Jun 2018 (actual)
- Study completion
- Oct 2018 (actual)
- First posted
- 4 Jan 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| FMT | Experimental | Biological: FMTFecal microbiota capsules (provided by Openbiome). Dosage: * Induction: 10 capsules (single dose) * Maintenance: 5 capsules, weekly, during 7 weeks. |
| Placebo | Placebo comparator | Other: PlaceboPlacebo capsules (provided by Openbiome). Dosage: * Induction: 10 capsules (single dose) * Maintenance: 5 capsules, weekly, during 7 weeks. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- On stable antiretroviral therapy with plasma HIV RNA <20 copies/mL during at least 48 weeks.
- CD4/CD8 ratio <1
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FMTCapsules with fecal microbiota from healthy donors | Biological | FMT |
| PlaceboPlacebo capsules | Other | Placebo |
Primary outcome
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: From baseline through week 48
12 secondary outcomes
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
Changes in CD4/CD8 ratio
Time frame: From baseline through week 48
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2018.
- Derived from this study: PubMed 33602945Serrano-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.
Related trials for HIV Infection
RecruitingObservational study
Olfactory Function and Model-Based Behavior in People Living With HIV and SUD
HIV, Substance Use Disorder
Not yet recruiting
Adapting the ESTEEM Intervention to Improve Mental Health and PrEP Uptake Among Men at Risk of HIV
PrEP Use
RecruitingPhase 2
Evaluating the Safety and Immunogenicity of MTBVAC
HIV I Infection, Tuberculosis
Active, not recruiting
Evaluating the Effectiveness of a Mobile HIV Prevention App to Increase HIV and Sexually Transmitted Infections (STI) Testing and PrEP Initiation Among Rural Men Who Have Sex With Men
HIV Infections, STI
Not yet recruiting
PNF RCT to Decrease Alcohol Use and Increase HIV Prevention
HIV (Human Immunodeficiency Virus), Alcohol Misuse
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing FMT in people with HIV Infection, run by Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 (time frame: From baseline through week 48). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03008941, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2018.