HIV-associated Enteropathy
Conditions
Brief summary
The purpose of the study is to evaluate the effectiveness of the oral nutritional therapy serum-derived bovine immunoglobulin protein isolate (SBI) 2.5 g twice a day (BID) and SBI 5.0 g versus placebo on supporting nutrient absorption in HIV+ subjects with HIV-associated enteropathy.
Detailed description
This study is evaluating the effectiveness of the oral nutritional therapy serum-derived bovine immunoglobulin protein isolate (SBI) 2.5g BID and SBI 5.0g compared to placebo for 6 months on gastrointestinal symptoms, nutritional status and quality of life in HIV+ subjects with HIV-associated enteropathy. In addition, the effects of SBI on pro-inflammatory intestinal microbial populations, bacterial translocation, intestinal barrier function, and systemic immune activation will be investigated.
Interventions
SBI is a specially formulated light-colored protein powder composed of immunoglobulin (IgG) and other serum proteins similar to those found in colostrum and milk. SBI does not contain any milk products such as lactose, casein, or whey. SBI is gluten-free, dye-free, and soy-free. SBI is manufactured in accordance with current Good Manufacturing Practice (cGMP) and FDA guidelines for medical food ingredients.
OTHERPlacebo
Matching placebo
Sponsors
Entera Health, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* History of HIV-1 infection * Plasma HIV viral load ≤40 copies/mL * Maintained virologic suppression for 1 year * Stable Antiretroviral Therapy (ART) regimen * History of HIV-associated diarrhea defined as abnormal passage of 3 or more unformed stools per day or a liquid stool volume greater than 200 g per day for at least 4 weeks duration
Exclusion criteria
* Positive stool test for pathogenic bacteria, C. difficile or ova and parasites * Conditions that require chronic therapy that is known to alter gut microbiota * Antibiotics within 2 weeks of screening (exception: prophylaxis antibiotics)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Daily Unformed Bowel Movements | Baseline and 4 weeks | Change in number of abnormal or unformed stools by week 4 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Peripheral CD4+ T Cell Counts in Lowest Baseline CD4+ Quartile (Less Than or Equal to 418) | Baseline and 4 weeks | Lowest baseline CD4+ quartile (less than or equal to 418) |
| Change From Baseline in Peripheral CD4+ T Cell Counts in 2nd Baseline CD4+ Quartile (Greater Than 418 and Less Than or Equal to 630 | Baseline and 4 weeks | 2nd Baseline CD4+ Quartile (greater than 418 and less than or equal to 630) |
| Change From Baseline in Peripheral CD4+ T Cell Counts in 3rd Baseline CD4+ Quartile (Greater Than 630 and Less Than or Equal to 890) | Baseline and 4 weeks | 3rd Baseline CD4+ Quartile (Greater than 630 and Less than or Equal to 893) |
| Change From Baseline in Peripheral CD4+ T Cell Counts in 4th Baseline CD4+ Quartile (Greater Than 893) | Baseline and 4 weeks | 4th Baseline CD4+ Quartile (greater than 893) |
| Change From Baseline in Duodenal Gut-associated Lymphoid Tissue (GALT) CD4+ T Cell Densities | Baseline and Week 24 | — |
Countries
United States
Participant flow
Pre-assignment details
Study consists of 2 phases, the Placebo-controlled (PC) phase and the Placebo-free (PF) extension phase. Participants were randomized in a 1:1:2:2 ratio into 4 groups: Placebo for 4 wk PC phase followed by either 2.5g or 5.0g BID for 20 wk PF phase or SBI 2.5g or 5.0g BID for 4-wk PC phase followed by 2.5g or 5.0g for 20 wk PF phase.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching Placebo | 36 |
| SBI 2.5 g Serum-derived bovine immunoglobulin protein isolate (SBI) 2.5 g
Serum-derived bovine immunoglobulin protein isolate (SBI): SBI is a specially formulated light-colored protein powder composed of immunoglobulin (IgG) and other serum proteins similar to those found in colostrum and milk. SBI does not contain any milk products such as lactose, casein, or whey. SBI is gluten-free, dye-free, and soy-free. SBI is manufactured in accordance with current Good Manufacturing Practice (cGMP) and FDA guidelines for medical food ingredients. | 34 |
| SBI 5.0g Serum-derived bovine immunoglobulin protein isolate (SBI)5.0g
Serum-derived bovine immunoglobulin protein isolate (SBI): SBI is a specially formulated light-colored protein powder composed of immunoglobulin (IgG) and other serum proteins similar to those found in colostrum and milk. SBI does not contain any milk products such as lactose, casein, or whey. SBI is gluten-free, dye-free, and soy-free. SBI is manufactured in accordance with current Good Manufacturing Practice (cGMP) and FDA guidelines for medical food ingredients. | 33 |
| Total | 103 |
Baseline characteristics
| Characteristic | SBI 5.0g | SBI 2.5 g | Total | Placebo |
|---|---|---|---|---|
| Age, Continuous | 50.7 years STANDARD_DEVIATION 8 | 50.9 years STANDARD_DEVIATION 6.7 | 51.1 years STANDARD_DEVIATION 7.1 | 51.8 years STANDARD_DEVIATION 6.8 |
| Baseline Plasma CD4+ cell count | 671 cells/microliter STANDARD_DEVIATION 319 | 746 cells/microliter STANDARD_DEVIATION 324 | 682 cells/microliter STANDARD_DEVIATION 317 | 629 cells/microliter STANDARD_DEVIATION 307 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 5 Participants | 11 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants | 29 Participants | 92 Participants | 32 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Plasma viral load | 28 copies/mL STANDARD_DEVIATION 28 | 27 copies/mL STANDARD_DEVIATION 22 | 26 copies/mL STANDARD_DEVIATION 21 | 24 copies/mL STANDARD_DEVIATION 11 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 22 Participants | 20 Participants | 63 Participants | 21 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 14 Participants | 38 Participants | 14 Participants |
| Sex: Female, Male Female | 11 Participants | 13 Participants | 32 Participants | 8 Participants |
| Sex: Female, Male Male | 22 Participants | 21 Participants | 71 Participants | 28 Participants |
| Years with HIV | 17.9 years STANDARD_DEVIATION 6.3 | 16.9 years STANDARD_DEVIATION 6.3 | 16.9 years STANDARD_DEVIATION 6.76 | 16 years STANDARD_DEVIATION 7.6 |
| Years with HIV-associated diarrhea | 6.6 years STANDARD_DEVIATION 6.7 | 6.9 years STANDARD_DEVIATION 7.3 | 5.9 years STANDARD_DEVIATION 6.54 | 4.4 years STANDARD_DEVIATION 5.4 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 26 / 55 | 20 / 47 |
| serious Total, serious adverse events | 2 / 55 | 1 / 47 |
Outcome results
Primary
Frequency of Daily Unformed Bowel Movements
Change in number of abnormal or unformed stools by week 4
Time frame: Baseline and 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Frequency of Daily Unformed Bowel Movements | -2.46 abnormal or unformed stools | Standard Deviation 2.01 |
| SBI 2.5 g | Frequency of Daily Unformed Bowel Movements | -2.16 abnormal or unformed stools | Standard Deviation 2.18 |
| SBI 5.0g | Frequency of Daily Unformed Bowel Movements | -2.20 abnormal or unformed stools | Standard Deviation 1.99 |
Other Pre-specified
Change From Baseline in Duodenal Gut-associated Lymphoid Tissue (GALT) CD4+ T Cell Densities
Time frame: Baseline and Week 24
Population: Sub-study
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Change From Baseline in Duodenal Gut-associated Lymphoid Tissue (GALT) CD4+ T Cell Densities | 144.80 cells/mm3 |
| SBI 2.5 g | Change From Baseline in Duodenal Gut-associated Lymphoid Tissue (GALT) CD4+ T Cell Densities | -67.95 cells/mm3 |
Other Pre-specified
Change From Baseline in Peripheral CD4+ T Cell Counts in 2nd Baseline CD4+ Quartile (Greater Than 418 and Less Than or Equal to 630
2nd Baseline CD4+ Quartile (greater than 418 and less than or equal to 630)
Time frame: Baseline and 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Peripheral CD4+ T Cell Counts in 2nd Baseline CD4+ Quartile (Greater Than 418 and Less Than or Equal to 630 | 31.46 cells/microliter | Standard Deviation 122.7 |
| SBI 2.5 g | Change From Baseline in Peripheral CD4+ T Cell Counts in 2nd Baseline CD4+ Quartile (Greater Than 418 and Less Than or Equal to 630 | 82.67 cells/microliter | Standard Deviation 205.16 |
| SBI 5.0g | Change From Baseline in Peripheral CD4+ T Cell Counts in 2nd Baseline CD4+ Quartile (Greater Than 418 and Less Than or Equal to 630 | 12.00 cells/microliter | Standard Deviation 119.75 |
Other Pre-specified
Change From Baseline in Peripheral CD4+ T Cell Counts in 3rd Baseline CD4+ Quartile (Greater Than 630 and Less Than or Equal to 890)
3rd Baseline CD4+ Quartile (Greater than 630 and Less than or Equal to 893)
Time frame: Baseline and 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Peripheral CD4+ T Cell Counts in 3rd Baseline CD4+ Quartile (Greater Than 630 and Less Than or Equal to 890) | 48.00 cells/microliter | — |
| SBI 2.5 g | Change From Baseline in Peripheral CD4+ T Cell Counts in 3rd Baseline CD4+ Quartile (Greater Than 630 and Less Than or Equal to 890) | 36.70 cells/microliter | Standard Deviation 183.14 |
| SBI 5.0g | Change From Baseline in Peripheral CD4+ T Cell Counts in 3rd Baseline CD4+ Quartile (Greater Than 630 and Less Than or Equal to 890) | -29.46 cells/microliter | Standard Deviation 224.83 |
Other Pre-specified
Change From Baseline in Peripheral CD4+ T Cell Counts in 4th Baseline CD4+ Quartile (Greater Than 893)
4th Baseline CD4+ Quartile (greater than 893)
Time frame: Baseline and 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Peripheral CD4+ T Cell Counts in 4th Baseline CD4+ Quartile (Greater Than 893) | -144.00 cells/microliter | Standard Deviation 155.15 |
| SBI 2.5 g | Change From Baseline in Peripheral CD4+ T Cell Counts in 4th Baseline CD4+ Quartile (Greater Than 893) | -54.20 cells/microliter | Standard Deviation 230.43 |
| SBI 5.0g | Change From Baseline in Peripheral CD4+ T Cell Counts in 4th Baseline CD4+ Quartile (Greater Than 893) | -365.25 cells/microliter | Standard Deviation 464.04 |
Other Pre-specified
Change From Baseline in Peripheral CD4+ T Cell Counts in Lowest Baseline CD4+ Quartile (Less Than or Equal to 418)
Lowest baseline CD4+ quartile (less than or equal to 418)
Time frame: Baseline and 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Peripheral CD4+ T Cell Counts in Lowest Baseline CD4+ Quartile (Less Than or Equal to 418) | -19.8 cells/microliter | Standard Deviation 59.22 |
| SBI 2.5 g | Change From Baseline in Peripheral CD4+ T Cell Counts in Lowest Baseline CD4+ Quartile (Less Than or Equal to 418) | 41.86 cells/microliter | Standard Deviation 84.83 |
| SBI 5.0g | Change From Baseline in Peripheral CD4+ T Cell Counts in Lowest Baseline CD4+ Quartile (Less Than or Equal to 418) | 47.63 cells/microliter | Standard Deviation 42.63 |