Cognitive Deterioration, Inflammation
Conditions
Brief summary
The purpose of this study is to investigate how recombinant human lactoferrin (rhLF) which is a partially iron saturated form of lactoferrin produced and purified from rice grain may improve mobility and memory in older adults with chronic inflammation. Lactoferrin, is a known multifunctional protein, and has been shown to have anti-inflammatory effects. A recombinant human version of this protein was recently developed and produced from rice. This is now available from the Ventria Bioscience Company in a controlled, pharmaceutical grade capsule. As part of this double blinded and randomized study, participants will take daily dosages of recombinant human lactoferrin (rhLF) or its matched placebo; to measure the effects of rhlactoferrin on chronic inflammation and its association with improving mobility and memory over a 6 month time period. During the study all participants will be asked to provide blood samples and will have physical and cognitive tests administered to them. By measuring biomarkers in the blood as well as changes in physical and cognitive measures, the investigators will gain an understanding of how rhlactoferrin may safely improve measures of chronic inflammation in older adults. As well as a better understanding of whether it has the potential to meaningfully influence important measures of physical and cognitive function known to be influenced by Chronic Inflammation (CI).
Detailed description
The primary objective of this study is to examine in a double blinded and randomized trial the efficacy of Recombinant Human lactoferrin (rhLF) in reducing chronic inflammation as measured by IL-6 and sTNFR1 in the bloodstream. The primary end point is to gather information about the tolerability of and adherence to oral rhlactoferrin (rhLF) among older adults with CI over a six-month period. The exploratory objective is to assess the efficacy of rhlactoferrin (rhLF) in attenuating cognitive decline as measured by the Digit Symbol Substitution Test and Trail Making Test, as well as improving physical mobility as measured by performance on 4 meter and six-minute walk tests. Further physical and functional measurement data will be gather using an Acti-graph link Activity monitor, the raw data collected will be used to : (i) characterize cumulative daily activity, (ii) assess daily circadian patterns of activity, (iii) assess physical activity variability, (iv) model patterns of daily activity, and (iv) estimate walking speed. This additional data will complement mobility measures by describing function enacted in daily life
Interventions
DRUGrhLactoferrin
Eligible participants will be provided with Recombinant Human lactoferrin (rhLF) in 250 mg capsules along with detailed instructions for taking the study drug and they will be asked to take six 250 mg capsules twice a day and to keep a daily dosing dairy.
OTHERPlacebo
Eligible participant will be provided with placebo in capsules of 250 mg along with detailed instructions for taking the placebo. Participants will be asked to take six 250 mg capsules twice a day and to keep a daily dosing dairy.
Sponsors
Ventria Bioscience
National Institute on Aging (NIA)
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
•Randomized: Participants are assigned to intervention groups by chance
Eligibility
Sex/Gender
ALL
Age
70 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 70 and older * able to complete 4- meter timed walk; walking speed \<1.0 m/sec * serum IL-6 level ≥ 2.5 pg/ml or TNFR1 level ≥1500 pg/ml
Exclusion criteria
* Daily anti-inflammatory drug use (prednisone, Advil, Aleve, Remicade, Enbrel, methotrexate, standing nonsteroidal anti-inflammatory drugs (NSAID), aspirin greater than 325 mg per day) * lower extremity mobility disability caused by Parkinson's disease, * cerebral vascular accident (CVA) with residual motor deficit, * severe osteoarthritis or rheumatoid arthritis * symptomatic claudication * hospitalization within 3 months for myocardial infarction (MI), angina, infection requiring antibiotics, or joint replacement. * Mini-Mental State Examination (MMSE) \< 21. * Lactose intolerant * allergy or intolerance to bovine products * being a vegan (since vegans will want to avoid Bovine products.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Effect of Rhlactoferrin on Serum Levels of Interleukin-6 (IL-6) | Baseline and 6 months | The effect of rhlactoferrin on serum levels (picogram/milliliter) of Interleukin-6 (IL-6) will be assessed as a measure of the percentage change of IL-6 serum levels from baseline |
| The Effect of Rhlactoferrin on Serum Levels of Tumor Necrosis Factor Alpha Receptor 1 (TNFR1) | From baseline to 6 months | The effect of rhlactoferrin on serum levels (picogram/milliliter) of tumor necrosis factor alpha receptor 1 (TNFR1) assessed as a measure of the percentage change of serum TNFR1 levels from baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Physical Mobility as Measured by 4 Meter Walk Test | At 6 months | A standard measurement of 4 meters is marked on a flat, long floor surface. The test taker is asked to walk the length at their usual pace while the test giver is recording the time with a stop watch. This test is repeated twice, and the average of the two recorded times is used as the data point. |
| Physical Mobility as Measured by 6 Minute Walk Test | At 6 months | A measured course is set up in an open area on a hard flat surface. The test taker walks on this measured course for 6 minutes, and the test administrators calculates the distance traveled over 6 minutes. The test taker is allowed to rest as is needed. |
| Attenuating Cognitive Decline as Measured by the Digital Symbol Substitution Test | At 6 months | The test taker is given a key consisting of numbers 1-9 that are paired with a unique symbol. The test taker is allowed 90 seconds to assign the correct symbol to the number on the list. The test administrator then scores the number of correct answers over the 90 second test time, and assigns a total score based on one point for each correct answer and therefore a higher score is a better outcome. |
| Physical Strength as Measured by Grip Strength | At 6 months | Hand grip strength is measured by the amount of static force that the hand can squeeze around a dynamometer. An administrator recorded the reading on the device. The force was measured in kilograms. |
| Tolerability of Oral rhLactoferrin as Assessed by Patient Diary of Total Number of Side Effects | From baseline through 6 months. | Study coordinators administered side effect questionnaire at each visit and via phone every two weeks during the treatment period. |
| Attenuating Cognitive Decline as Measured by the Trail Making Test A and B. | At 6 months | For test A, the test taker is given a sheet of paper that has the numbers 1-25 within individual circles randomly distributed on the page. The test taker is asked to connect the numbers sequentially over a period of 4 minutes (240 seconds). The score is recorded as the time it takes to complete the task in seconds. For test B, the test taker is given a piece of paper that has numbers 1-13 and letters A-L. Each letter or number is inside of a circle. The test taker must then draw a line from one circled number to the next circled letter (ie. 1 to A to 2 to B to 3 to C etc.) over a period of 6 minutes (360 seconds). The time it takes to complete this task is recorded in seconds. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| rhLactoferrin rH lactoferrin will be provided by Ventria Biosciences. Each capsule will contain 250 mg of rH lactoferrin as active ingredient. Subjects will receive 1500 mg of lactoferrin in capsule form twice a day. Dosing will be six 250 mg capsules twice a day for six months.
rhLactoferrin: Eligible participants will be provided with Recombinant Human lactoferrin (rhLF) in 250 mg capsules along with detailed instructions for taking the study drug and they will be asked to take six 250 mg capsules twice a day and to keep a daily dosing dairy. | 18 |
| Placebo Matching placebo capsule will be provided by Ventria Biosciences and six capsules twice a day will be provided to the subjects in this arm.
Placebo: Eligible participant will be provided with placebo in capsules of 250 mg along with detailed instructions for taking the placebo. Participants will be asked to take six 250 mg capsules twice a day and to keep a daily dosing dairy. | 18 |
| Total | 36 |
Baseline characteristics
| Characteristic | rhLactoferrin | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 18 Participants | 18 Participants | 36 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 82.6 years STANDARD_DEVIATION 6.6 | 79.6 years STANDARD_DEVIATION 5.6 | 81.1 years STANDARD_DEVIATION 6.21 |
| Attenuating cognitive decline as measured by the digital symbol substitution test | 33 Correct answers STANDARD_DEVIATION 12 | 31 Correct answers STANDARD_DEVIATION 10 | 32 Correct answers STANDARD_DEVIATION 11 |
| Attenuating cognitive decline as measured by the trail making test A and B Test A | 48.3 seconds STANDARD_DEVIATION 16.7 | 54.1 seconds STANDARD_DEVIATION 28.9 | 51.1 seconds STANDARD_DEVIATION 23.3 |
| Attenuating cognitive decline as measured by the trail making test A and B Test B | 101.1 seconds STANDARD_DEVIATION 34.6 | 109.3 seconds STANDARD_DEVIATION 49.3 | 104.9 seconds STANDARD_DEVIATION 41.7 |
| BMI BMI < 30 | 13 Participants | 10 Participants | 23 Participants |
| BMI BMI ≥ 30 | 5 Participants | 8 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants | 17 Participants | 34 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Log Total Activity Count | 14.26 Log Total Activity Count STANDARD_DEVIATION 0.35 | 14.46 Log Total Activity Count STANDARD_DEVIATION 0.28 | 14.35 Log Total Activity Count STANDARD_DEVIATION 0.33 |
| Physical mobility as measured by 4 meter walk test | 0.78 m/sec STANDARD_DEVIATION 0.17 | 0.78 m/sec STANDARD_DEVIATION 0.13 | 0.78 m/sec STANDARD_DEVIATION 0.15 |
| Physical mobility as measured by 6 minute walk test | 358.9 meters STANDARD_DEVIATION 124.3 | 345.8 meters STANDARD_DEVIATION 88.9 | 352.3 meters STANDARD_DEVIATION 106.6 |
| Physical strength as measured by grip strength | 26.2 kg STANDARD_DEVIATION 7.3 | 25.3 kg STANDARD_DEVIATION 6.7 | 25.8 kg STANDARD_DEVIATION 6.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 15 Participants | 29 Participants |
| Sex: Female, Male Female | 11 Participants | 11 Participants | 22 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 18 |
| other Total, other adverse events | 13 / 18 | 15 / 18 |
| serious Total, serious adverse events | 0 / 18 | 1 / 18 |
Outcome results
Primary
The Effect of Rhlactoferrin on Serum Levels of Interleukin-6 (IL-6)
The effect of rhlactoferrin on serum levels (picogram/milliliter) of Interleukin-6 (IL-6) will be assessed as a measure of the percentage change of IL-6 serum levels from baseline
Time frame: Baseline and 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rhLactoferrin | The Effect of Rhlactoferrin on Serum Levels of Interleukin-6 (IL-6) | -0.640 Percent change of IL-6 | Standard Deviation 1.137 |
| Placebo | The Effect of Rhlactoferrin on Serum Levels of Interleukin-6 (IL-6) | 0.932 Percent change of IL-6 | Standard Deviation 0.265 |
Primary
The Effect of Rhlactoferrin on Serum Levels of Tumor Necrosis Factor Alpha Receptor 1 (TNFR1)
The effect of rhlactoferrin on serum levels (picogram/milliliter) of tumor necrosis factor alpha receptor 1 (TNFR1) assessed as a measure of the percentage change of serum TNFR1 levels from baseline
Time frame: From baseline to 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rhLactoferrin | The Effect of Rhlactoferrin on Serum Levels of Tumor Necrosis Factor Alpha Receptor 1 (TNFR1) | 19.709 Percent change from baseline | Standard Deviation 85.084 |
| Placebo | The Effect of Rhlactoferrin on Serum Levels of Tumor Necrosis Factor Alpha Receptor 1 (TNFR1) | 140.748 Percent change from baseline | Standard Deviation 43.24 |
Secondary
Attenuating Cognitive Decline as Measured by the Digital Symbol Substitution Test
The test taker is given a key consisting of numbers 1-9 that are paired with a unique symbol. The test taker is allowed 90 seconds to assign the correct symbol to the number on the list. The test administrator then scores the number of correct answers over the 90 second test time, and assigns a total score based on one point for each correct answer and therefore a higher score is a better outcome.
Time frame: At 6 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| rhLactoferrin | Attenuating Cognitive Decline as Measured by the Digital Symbol Substitution Test | 31.61 correct responses |
| Placebo | Attenuating Cognitive Decline as Measured by the Digital Symbol Substitution Test | 31 correct responses |
Secondary
Attenuating Cognitive Decline as Measured by the Trail Making Test A and B.
For test A, the test taker is given a sheet of paper that has the numbers 1-25 within individual circles randomly distributed on the page. The test taker is asked to connect the numbers sequentially over a period of 4 minutes (240 seconds). The score is recorded as the time it takes to complete the task in seconds. For test B, the test taker is given a piece of paper that has numbers 1-13 and letters A-L. Each letter or number is inside of a circle. The test taker must then draw a line from one circled number to the next circled letter (ie. 1 to A to 2 to B to 3 to C etc.) over a period of 6 minutes (360 seconds). The time it takes to complete this task is recorded in seconds.
Time frame: At 6 months
Population: A total of 36 participants entered the study. One participant in the placebo group later dropped out and therefore was not included in the analysis. One additional participant in the placebo group was unable to complete Trail Making Test B, so they were not included in the analysis.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| rhLactoferrin | Attenuating Cognitive Decline as Measured by the Trail Making Test A and B. | Trail Making Test A | 33.11 seconds |
| rhLactoferrin | Attenuating Cognitive Decline as Measured by the Trail Making Test A and B. | Trail Making Test B | 122.73 seconds |
| Placebo | Attenuating Cognitive Decline as Measured by the Trail Making Test A and B. | Trail Making Test A | 42.68 seconds |
| Placebo | Attenuating Cognitive Decline as Measured by the Trail Making Test A and B. | Trail Making Test B | 131.24 seconds |
Secondary
Physical Mobility as Measured by 4 Meter Walk Test
A standard measurement of 4 meters is marked on a flat, long floor surface. The test taker is asked to walk the length at their usual pace while the test giver is recording the time with a stop watch. This test is repeated twice, and the average of the two recorded times is used as the data point.
Time frame: At 6 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| rhLactoferrin | Physical Mobility as Measured by 4 Meter Walk Test | 0.786 m/sec |
| Placebo | Physical Mobility as Measured by 4 Meter Walk Test | 0.767 m/sec |
Secondary
Physical Mobility as Measured by 6 Minute Walk Test
A measured course is set up in an open area on a hard flat surface. The test taker walks on this measured course for 6 minutes, and the test administrators calculates the distance traveled over 6 minutes. The test taker is allowed to rest as is needed.
Time frame: At 6 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| rhLactoferrin | Physical Mobility as Measured by 6 Minute Walk Test | 359.66 meter |
| Placebo | Physical Mobility as Measured by 6 Minute Walk Test | 334.94 meter |
Secondary
Physical Strength as Measured by Grip Strength
Hand grip strength is measured by the amount of static force that the hand can squeeze around a dynamometer. An administrator recorded the reading on the device. The force was measured in kilograms.
Time frame: At 6 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| rhLactoferrin | Physical Strength as Measured by Grip Strength | 23.493 kg |
| Placebo | Physical Strength as Measured by Grip Strength | 20.294 kg |
Secondary
Tolerability of Oral rhLactoferrin as Assessed by Patient Diary of Total Number of Side Effects
Study coordinators administered side effect questionnaire at each visit and via phone every two weeks during the treatment period.
Time frame: From baseline through 6 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rhLactoferrin | Tolerability of Oral rhLactoferrin as Assessed by Patient Diary of Total Number of Side Effects | 2.23 Side effects/100 treatment days | Standard Deviation 3.16 |
| Placebo | Tolerability of Oral rhLactoferrin as Assessed by Patient Diary of Total Number of Side Effects | 4.77 Side effects/100 treatment days | Standard Deviation 4.23 |