HIV Infection
Conditions
Brief summary
Our general goal is to evaluate the potential effectiveness of recombinant lactoferrin (1500mg bid) for reducing inflammation among HIV positive participants.
Interventions
DRUGRecombinant Lactoferrin
DRUGPlacebo
Sponsors
Ventria Bioscience
Jason Baker
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. HIV-positive participants receiving Antiretroviral Therapy (ART) for \>1 year 2. HIV RNA level \<200 copies/mL for at least 6 months (≥2 separate values) 3. Age \>40 years
Exclusion criteria
1. Prior cardiovascular disease or stroke 2. Diabetes 3. Rheumatologic Diseases 4. Pregnancy 5. Chronic kidney disease, stage IV or V (creatinine clearance \<30 mL/min/1.73m2) 6. Cirrhosis or end-stage liver disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With at Least One Side Effect, Adverse Event, and Serious Adverse Event | During 3 months on Lactoferrin or Placebo (and following washout period) | Self reported side effects and/or Division of AIDS (DAIDS) criteria will be used for grading adverse events (serious and non-serious) |
| IL-6 & D-dimer Score Changes From Baseline to 3 Months (or Month 5 to Month 8) | 3 months (Baseline to Month 3 or Month 5 to Month 8) | The IL-6 & D-dimer score is defined as: 0. 33\*log2 IL-6 + 0.16\*log2 D-dimer, where IL-6 is measured in pg/mL and D-dimer in ug/mL. Since the biomarkers are on the log2 scale, associations of risk with the IL-6 & D-dimer score are interpreted as HR(event) per doubling of IL-6 and D-dimer, or HR(event) per 20% increase in IL-6 and D-dimer; the score itself is unitless. Among the 3766 study participants for whom the score was developed, the min was -1.7, the max was 2.5. Higher scores are worse. |
| Number of Participants Taking Medication as Assigned | 3 months | Number of participants taking medication as assigned at 3 months |
Other
| Measure | Time frame | Description |
|---|---|---|
| Activated Monocyte Phenotype (CD16+) | 3 months | The change in CD16+ monocyte subsets will be compared between active and placebo treatment phases. During both the active and placebo treatment phase, all relevant time points are used in calculation of change (i.e., baseline, month 1 and month 3 for phase 1; and similarly months 5, 6 and 8 for phase 2). |
| sCD163 | 3 months | The change in blood levels of sCD163 will be compared between active and placebo treatment phases. During both the active and placebo treatment phase, all relevant time points are used in calculation of change (i.e., baseline, month 1 and month 3 for phase 1; and similarly months 5, 6 and 8 for phase 2). |
Countries
United States
Participant flow
Pre-assignment details
One participant was administratively withdrawn prior to receiving medication.
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population Includes groups randomized to receive placebo first and active drug first. | 54 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Period | Withdrawal by Subject | 1 | 3 |
| Washout | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 51 Participants |
| Age, Continuous | 51.6 years STANDARD_DEVIATION 7 |
| Diastolic Blood Pressure At Enrollment | 79.5 mm HG STANDARD_DEVIATION 10.5 |
| Diastolic Blood Pressure Beginning of Lactoferrin | 79.3 mm HG STANDARD_DEVIATION 10.2 |
| Diastolic Blood Pressure Beginning of Placebo Treatment | 78.6 mm HG STANDARD_DEVIATION 9.9 |
| Interleukin-6 and D-Dimer Score At Enrollment | -0.00 scores on a scale STANDARD_DEVIATION 0.38 |
| Interleukin-6 and D-Dimer Score Beginning of Lactoferrin Treatment | -0.02 scores on a scale STANDARD_DEVIATION 0.45 |
| Interleukin-6 and D-Dimer Score Beginning of Placebo Treatment | 0.02 scores on a scale STANDARD_DEVIATION 0.39 |
| Large Artery Elasticity At Enrollment | 16.77 mL/mmHg x 10 STANDARD_DEVIATION 5.74 |
| Large Artery Elasticity Beginning of Lactoferrin Treatment | 16.89 mL/mmHg x 10 STANDARD_DEVIATION 5.48 |
| Large Artery Elasticity Beginning of Placebo Treatment | 17.02 mL/mmHg x 10 STANDARD_DEVIATION 5.56 |
| Monocyte CD16+ At Enrollment | 10.55 percent of total monocyte population STANDARD_DEVIATION 7.11 |
| Monocyte CD16+ Beginning of Lactoferrin Treatment | 11.96 percent of total monocyte population STANDARD_DEVIATION 9.56 |
| Monocyte CD16+ Beginning of Placebo Treatment | 10.41 percent of total monocyte population STANDARD_DEVIATION 7.56 |
| Race/Ethnicity, Customized African American | 11 Participants |
| Race/Ethnicity, Customized Hispanic | 2 Participants |
| Race/Ethnicity, Customized Other | 2 Participants |
| Race/Ethnicity, Customized White | 39 Participants |
| sCD163 At Enrollment | 0.21 mg/L STANDARD_DEVIATION 0.12 |
| sCD163 Beginning of Lactoferrin Treatment | 0.19 mg/L STANDARD_DEVIATION 0.1 |
| sCD163 Beginning of Placebo Treatment | 0.23 mg/L STANDARD_DEVIATION 0.15 |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 48 Participants |
| Small Artery Elasticity At Enrollment | 6.49 mL/mmHg x 100 STANDARD_DEVIATION 2.91 |
| Small Artery Elasticity Beginning of Lactoferrin Treatment | 6.61 mL/mmHg x 100 STANDARD_DEVIATION 2.87 |
| Small Artery Elasticity Beginning of Placebo Treatment | 6.79 mL/mmHg x 100 STANDARD_DEVIATION 3.04 |
| Systolic Blood Pressure At Enrollment | 129.7 mm Hg STANDARD_DEVIATION 15.4 |
| Systolic Blood Pressure Beginning of Lactoferrin Treatment | 127.8 mm Hg STANDARD_DEVIATION 15.6 |
| Systolic Blood Pressure Beginning of Placebo Treatment | 128.0 mm Hg STANDARD_DEVIATION 14.9 |
| Weight | 190.0 pounds STANDARD_DEVIATION 38.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 54 | 0 / 54 |
| other Total, other adverse events | 10 / 54 | 10 / 54 |
| serious Total, serious adverse events | 5 / 54 | 1 / 54 |
Outcome results
Primary
IL-6 & D-dimer Score Changes From Baseline to 3 Months (or Month 5 to Month 8)
The IL-6 & D-dimer score is defined as: 0. 33\*log2 IL-6 + 0.16\*log2 D-dimer, where IL-6 is measured in pg/mL and D-dimer in ug/mL. Since the biomarkers are on the log2 scale, associations of risk with the IL-6 & D-dimer score are interpreted as HR(event) per doubling of IL-6 and D-dimer, or HR(event) per 20% increase in IL-6 and D-dimer; the score itself is unitless. Among the 3766 study participants for whom the score was developed, the min was -1.7, the max was 2.5. Higher scores are worse.
Time frame: 3 months (Baseline to Month 3 or Month 5 to Month 8)
Population: 45 participants contributed data during phase two. Participants had to attend the first visit (baseline or month 5) and also one follow-up visit in order to contribute data to the analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | IL-6 & D-dimer Score Changes From Baseline to 3 Months (or Month 5 to Month 8) | -0.02 score on a scale | Standard Deviation 0.39 |
| Recombinant Lactoferrin | IL-6 & D-dimer Score Changes From Baseline to 3 Months (or Month 5 to Month 8) | 0.06 score on a scale | Standard Deviation 0.36 |
p-value: 0.38t-test, 2 sided
Primary
Number of Participants Taking Medication as Assigned
Number of participants taking medication as assigned at 3 months
Time frame: 3 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Taking Medication as Assigned | 40 Participants |
| Recombinant Lactoferrin | Number of Participants Taking Medication as Assigned | 38 Participants |
Primary
Number of Participants With at Least One Side Effect, Adverse Event, and Serious Adverse Event
Self reported side effects and/or Division of AIDS (DAIDS) criteria will be used for grading adverse events (serious and non-serious)
Time frame: During 3 months on Lactoferrin or Placebo (and following washout period)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With at Least One Side Effect, Adverse Event, and Serious Adverse Event | At least one side effect | 20 Participants |
| Placebo | Number of Participants With at Least One Side Effect, Adverse Event, and Serious Adverse Event | At least one adverse event (includes SAE) | 12 Participants |
| Placebo | Number of Participants With at Least One Side Effect, Adverse Event, and Serious Adverse Event | At least one Serious Adverse Event | 5 Participants |
| Recombinant Lactoferrin | Number of Participants With at Least One Side Effect, Adverse Event, and Serious Adverse Event | At least one side effect | 17 Participants |
| Recombinant Lactoferrin | Number of Participants With at Least One Side Effect, Adverse Event, and Serious Adverse Event | At least one adverse event (includes SAE) | 11 Participants |
| Recombinant Lactoferrin | Number of Participants With at Least One Side Effect, Adverse Event, and Serious Adverse Event | At least one Serious Adverse Event | 1 Participants |
Other Pre-specified
Activated Monocyte Phenotype (CD16+)
The change in CD16+ monocyte subsets will be compared between active and placebo treatment phases. During both the active and placebo treatment phase, all relevant time points are used in calculation of change (i.e., baseline, month 1 and month 3 for phase 1; and similarly months 5, 6 and 8 for phase 2).
Time frame: 3 months
Population: 45 participants contributed data during phase two. Participants had to attend the first visit (baseline or month 5) and also one follow-up visit in order to contribute data to the analyses. Fewer participants had pre-drug and post-drug cells collected so numbers are less than 45 for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Activated Monocyte Phenotype (CD16+) | -0.45 percent of total monocyte population | Standard Deviation 5.44 |
| Recombinant Lactoferrin | Activated Monocyte Phenotype (CD16+) | -1.42 percent of total monocyte population | Standard Deviation 9.26 |
p-value: 0.55t-test, 2 sided
Other Pre-specified
sCD163
The change in blood levels of sCD163 will be compared between active and placebo treatment phases. During both the active and placebo treatment phase, all relevant time points are used in calculation of change (i.e., baseline, month 1 and month 3 for phase 1; and similarly months 5, 6 and 8 for phase 2).
Time frame: 3 months
Population: 45 participants contributed data during phase two. Participants had to attend the first visit (baseline or month 5) and also one follow-up visit in order to contribute data to the analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | sCD163 | -0.01 mg/L | Standard Deviation 0.06 |
| Recombinant Lactoferrin | sCD163 | 0.03 mg/L | Standard Deviation 0.11 |
p-value: 0.1t-test, 2 sided