Pilot Study of GLY-LOW Supplementation in Postmenopausal Women With Obesity

Obesity Clinical Trial

Official title:

Pilot Study of GLY-LOW Supplementation in Postmenopausal Women With Obesity

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06242535
• Other study ID #: BRANY IRB # 23-02-452-1498
• Status: Active, not recruiting
• Phase: Early Phase 1
• Start date: July 27, 2023
• Est. completion date: July 27, 2024

Study information

• Verified date: June 2024
• Source: Hoskinson Health and Wellness Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A combination of generally regarded as safe (GRAS) compounds named GLY-LOW, which included:

alpha lipoic acid, pyridoxamine, nicotinamide, piperine and thiamine, were examined in pre-clinical experiments. GLY-LOW supplementation reduced caloric intake and increased insulin sensitivity in mice. In female mice, GLY-LOW supplementation reversed aging-related declines in female hormones. Studies in humans are needed to examine the feasibility, utility and efficacy of GLY-LOW supplementation in post-menopausal women with obesity toward improving aging-related impairments. The effect of GLY-LOW supplementation on these obesity and biological age-related impairments in post-menopausal adult female humans with obesity is unknown. We aim to translate the findings of GLY-LOW supplementation in animals to a cohort of healthy, postmenopausal females at birth with obesity by conducting a one-group, no-placebo comparer, pre post intervention clinical trial. Additionally, we propose to examine the specific effect of supplementation by GLY-LOW on biological aging via retina scan. The objectives of the proposed pilot study are:

I. Conduct a 6-month pilot study to examine the feasibility, utility and efficacy of GLY-LOW supplementation in a total of 40 postmenopausal female born adults > 55 years with obesity (> 30 BMI)

Ia. Examine alterations in self-reported caloric intake and the following health and biological aging, parameters prior to and after 6 months of GLY-LOW supplementation:

1. Self-reported Caloric Intake

2. Metabolic disease risk

3. Cardiovascular disease risk

4. Metabolic assessments

5. Hormones

6. Physical Function and Fitness

7. Muscular strength

8. Cognitive Function and Depression assessments

9. Systemic inflammation

10. Biological aging

11. Safety parameters (also every 2 months during the intervention; ECG at baseline and 2 months only) 12, Compliance measures (pill counts and interviews every 2 months during the intervention)

Description:

Study Population:

Healthy, postmenopausal (> 1 year from last menstrual cycle) adult females (at birth), > 55 years of age with obesity (≥ 25 BMI)

Objectives/Purpose of the Study:

Worldwide rates of obesity increased from 100 million to 764 million between 1980 and 2021. During the same time frame, a five-fold increase in Type 2 diabetes (T2DM) was reported4. Increases were similar across the globe with older individuals at greatest risk of obesity and related metabolic dysfunction. Central obesity is well known to be both a manifestation and driver of metabolic syndrome5 with similar prevalence worldwide6. Older, post-menopausal females, in particular, are at increased risk of developing central obesity due to a reduction in endogenous ovarian hormone production7. Novel multi-modal therapies are needed to address central obesity-related metabolic dysfunction in post-menopausal females. However, current therapeutic methods lack specificity and propose universal solutions to a multi-factorial disorder requiring an individualized, precision medicine approach8. More concerning, is the lack of rigorous, scientific evidence to support conventional dietary therapies for reducing aging-related central obesity and associated metabolic dysfunction9. Targeting multiple biological pathways that are related to individual behavioral determinants (caloric intake) and biological aging markers (estrogen levels) may identify more precise therapies in post-menopausal female adults with obesity.

Recently, advanced glycation end-products (AGEs) were identified as potential drivers of obesity-related impaired metabolic function10. In a series of in vitro and in vivo experiments, a combination of GRAS compounds that function synergistically to improve metabolic health and extend lifespan [(alpha lipoic acid, pyridoxamine, nicotinamide, piperine and thiamine (i.e. GLY-LOW)] were examined11-13. Supplementation with GLY-LOW was shown to detoxify methylglyoxal (MGO), a reactive precursor to AGEs. In addition, GLY-LOW supplementation reduced caloric intake and glycolysis, reprogramed metabolism, and increased insulin sensitivity and mTor signaling in the hypothalamus of the mice. In female animals GLY-LOW supplementation reversed aging-related declines in estrogen and related female hormones. Studies in humans are needed to translate these findings and explore the feasibility, utility and efficacy of GLY-LOW supplementation in post-menopausal women with obesity toward improving aging-related impairments. These include increased metabolic disease risk and insufficiency, impaired physical function, osteoporosis, reduced fitness levels, cognitive impairment, systemic inflammation and premature biological aging. Interestingly, results of a novel biological aging assessment, retina scan, were recently shown to be associated with metabolic dysfunction via inflammatory pathways14. The effect of GLY-LOW supplementation on these obesity and biological age-related impairments in post-menopausal adult female humans with obesity is unknown.

Study Site:

The Hoskinson Health and Wellness Clinic (HHWC) focuses on your whole health for your whole life, and provides a proactive, not reactive, personalized and integrated, multi-component solution to age-related increases in obesity and associated declines in metabolic health. The HHWC utilizes functional, precision medicine to identify unhealthy aging biomarkers and genetic vulnerabilities, and innovative medical technology to both diagnose and manage aging-related metabolic, physical and cognitive impairments. State-of-the-art assessments identify targets for tailored programming including diet instruction, nutrition education and supplementation, fitness counseling and training. The HHWC proposes to conduct a series of clinical studies using these state-of-the-art measures of aging-related parameters. Initially, we aim to translate the findings of GLY-LOW supplementation in animals to a cohort of healthy, postmenopausal females at birth with obesity by conducting a one-group, no-placebo comparer, pre post intervention clinical trial. Additionally, we propose to examine the specific effect of supplementation by GLY-LOW on biological aging via retina scan. The objectives of the proposed pilot study are:

I. Conduct a 6-month pilot study to examine the feasibility, utility and efficacy of GLY-LOW supplementation in a total of 40 postmenopausal female born adults > 55 years with obesity (> 25 BMI)

Ia. Examine alterations in self-reported caloric intake and the following health and biological aging, parameters prior to and after 6 months of GLY-LOW supplementation:

1. Self-reported Caloric Intake

2. Metabolic disease risk

3. Cardiovascular disease risk

4. Metabolic assessments

5. Hormones

6. Physical Function and Fitness

7. Muscular strength

8. Cognitive Function and Depression assessments

9. Systemic inflammation

10. Biological aging

11. Safety parameters (also every 2 months during the intervention; ECG at baseline and 2 months only)

12. Compliance measures (pill counts and interviews every 2 months during the intervention)

Trial Design:

A. The Primary Endpoint of the study is metabolic disease risk

C. Design of the Trial:

One group, no-placebo comparer, pre post intervention clinical trial

D. Randomization and Blinding:

The one group, no-placebo comparer pilot study will not require randomization. Study data managers and biostatisticians will be blinded to basic demographic and clinical characteristics (e.g. female, postmenopausal) of the study population and the overall purpose of the trial.

Initial Recruitment/Screening, Enrollment, and Baseline Evaluation:

Recruitment, screening and enrollment will occur during the first eight weeks of the study. Approximately 40 participants will be screened and enrolled into the study. Participation in the baseline evaluation will occur during weeks 9-12 (Table 1). Recruitment will be by referrals, personal interview, brochure mail-outs to area physicians, community center flyers and presentations, presentations at civic meetings, mass media announcements, social media posts, as well as clinic screenings as currently used in our existing studies and clinical services at the Hoskinson Health and Wellness Center. The plan is described below:

1. Potential study participants will be provided with a general information handout or link to our website regarding the study and contact information for participation.

2. Study personnel will receive phone, email inquiries or website inquiries and conduct a pre-screening interview and complete a checklist to determine eligibility.

3. Study personnel and/or other medical staff will then conduct the IRB-approved informed consent procedures and begin the screening process for study participants. An explanation of all procedures, potential risks, temporary side effects, anticipated benefits, and alternative methods (nutrition and fitness counseling, weight loss pharmaceuticals or nutraceuticals, other anti-aging therapeutics) will be given to the study participant. Confidentiality is assured as well as the right not to participate or to withdraw at any time. The signature of the study participant will be obtained on the consent form. A copy of the forms will be given to each study participant. Assurance that all questions have been answered about the study testing is obtained from the participants. Names and telephone numbers of contact persons on the medical team are given to each study participant for use if future questions arise.

4. General health screenings will then be performed by qualified medical staff. A medical physical evaluation to verify eligibility will be performed at the intervention baseline visits and a list of current medications will be required.

5. After clearance by the study physician, the study participant will receive the first set of baseline measurements The study coordinator will schedule the second day of baseline measurements with the study participant. The study participant will be advised to fast for at least 12 hours prior to the second day of baseline testing

E. Treatment, Dosage and Dosing regimen of the GLY-LOW supplement:

This supplement is available for over-the-counter purchase2. Each capsule is a combination of vitamins and natural products: Vitamin B1 (100mg); Vitamin B6 (50mg); Niacin (200mg); Alpha Lipoic Acid (150mg); and Piperine (15mg). Each participant will take this supplement daily in a pill form orally once in the morning. The test product will be two capsules a day with breakfast between 7:00 - 11:00 AM. The chosen doses were based on dose conversion from mice to humans and the prior data on safety for each of the compounds in humans.

F. Description of the Dosage Form, Packaging and Labeling of the GLY-LOW supplement:

G. Expected Duration of Subject Participation: 34 weeks (Figure 1 - Consort Diagram)

I. Available Alternative Treatments offered at the HHWC include nutrition and fitness counseling, weight loss pharmaceuticals or nutraceuticals, other anti-aging therapeutics. Study participants will be provided with information concerning these alternative treatment therapies during the consent procedures.

Follow-up Assessments:

1. The study participant will attend a follow-up safety assessment visit every two months and will participate in blood tests and MSQ. ECG will be assessed at baseline and 2 months only.

2. The study participants will attend one follow-up assessment after 6 months of receiving the study supplement (GLY-LOW). Baseline measurements will be repeated during these follow-up assessments in order to examine the effectiveness of the intervention.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: July 27, 2024
• Est. primary completion date: July 27, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 56 Years and older

Eligibility

Inclusion Criteria:

• Post-menopausal (>1 year from last menstrual cycle) adult females (at birth) >55 years of age with obesity (BMI = 25)

Exclusion Criteria:

• Males

• Adults not females at birth

• Adult females diagnosed with Gout

• Adult females receiving hormone replacement therapy (HRT)

• Adult females who are currently prescribed or received weight loss medications within the past 6 months, or currently enrolled in a defined weight loss program.

• Adult females with cardio-metabolic disease [e.g. cardiovascular disease (CVD), type 2 diabetes (T2DM), hypertension, h/o stroke etc.)] requiring any prescription medication.

• Adult females with other chronic immune, pulmonary, neurodegenerative or systemic disease requiring prescription medication

• Adult females with severe asthma based upon American Thoracic Society (ATS) standards and/or NIH guidelines.

• Adult females requiring monoclonal antibody or biological treatment

• Adult females diagnosed with an acute lower respiratory or GI infection within 2 weeks

• Adult females who are pregnant (would not qualify as post-menopausal) or nursing mothers

• Adult females reporting moderate to severe mental or physical disability

• Adult females reporting unwillingness to travel to onsite clinical facilities

• Adult females with moderate to severe cognitive impairment

• Adult females diagnosed with an eating disorder

• Adult females on blood thinners and anti-platelet drugs (other than aspirin), on chronic steroids (including inhaled), on spironolactone, on statins, on diuretics, on chronic pain medications, on any medication that affects glucose, insulin, lipids, metabolic performance

• Adult females with any recent change in chronic disease or any recent change in medication.

• Adult females on supplements with potential to augment or compete with the GLY-LOW.

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Cognitive Impairment
• Depression
• Hormone Deficiency
• Hyperlipidemias
• Hyperphagia
• Hypertension
• Inflammation
• Insulin Resistance
• Obesity
• Overeating
• Physical Disability
• Physical Inactivity

Intervention

Biological:
• GLY-LOW
The supplement, GLY-LOW, is FDA approved for use as a dietary supplement (IND 162006)

Locations

Country	Name	City	State
United States	Hoskinson Health and Wellness Clinic	Gillette	Wyoming

Sponsors (3)

Lead Sponsor	Collaborator
Hoskinson Health and Wellness Clinic	Buck Institute for Research on Aging, University of Wyoming

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Safety Outcomes	Safety outcomes will obtained baseline, every 2-months and at 3 months during the intervention and at 6-month follow-up as described. These include: 1) measurement of Thyroid Stimulation Hormone (TSH), Follicle-Stimulating Hormone (FSH), Luteinizing Hormone (LH) and blood platelet counts, 2) measurement of cardiac function by Electrocardiogram (ECG), 3) administration of the medical symptoms questionnaire (MSQ)	during the screening/baseline visit and again during the 6-month follow-up visit.
Primary	Insulin Resistance (IR)	Measured by examining biochemical markers using samples of whole blood obtained in a certified laboratory. . Study participants will be required to fast for 12 hours prior to the blood test. Blood collection and processing: Venous blood will be collected in the morning after a 12 hour fast with the study participant seated. Blood will be collected in tubes containing 1.5 mg/ml EDTA for procedures requiring plasma, in tubes with no additives for serum measures and citrate tubes for homeostasis endpoints.	during the screening/baseline visit and again during the 6-month follow-up visit.
Primary	Fasting Insulin (I) and Glucose (G)	Measured by examining biochemical markers using samples of whole blood obtained in a certified laboratory. . Study participants will be required to fast for 12 hours prior to the blood test. Blood collection and processing: Venous blood will be collected in the morning after a 12 hour fast with the study participant seated. Blood will be collected in tubes containing 1.5 mg/ml EDTA for procedures requiring plasma, in tubes with no additives for serum measures and citrate tubes for homeostasis endpoints.	during the screening/baseline visit and again during the 6-month follow-up visit.
Primary	Glycosylated Hemoglobin [Hemoglobin A1C (HBA1C)]	Measured by examining biochemical markers using samples of whole blood obtained in a certified laboratory. . Study participants will be required to fast for 12 hours prior to the blood test. Blood collection and processing: Venous blood will be collected in the morning after a 12 hour fast with the study participant seated. Blood will be collected in tubes containing 1.5 mg/ml EDTA for procedures requiring plasma, in tubes with no additives for serum measures and citrate tubes for homeostasis endpoints.	during the screening/baseline visit and again during the 6-month follow-up visit.
Secondary	Dietary Intake	assessed using the ASA24-2022 Dietary Assessment Tool. Study participants will complete a 24hr food recall. Study personnel will download, process, and analyze the ASA24 data per NCI protocols.	during the screening/baseline visit and again during the 6-month follow-up visit.study participants will complete a 24hr food recall as recommended16. Study personnel will download, process, and analyze the ASA24 data per NCI protocols
Secondary	Total Cholesterol, Low Density Lipoprotein (LDL), High Density Lipoprotein (HDL) and triglycerides (TRI) and Systolic (SBP) and Diastolic Blood Pressure (DPB)	Measured by examining biochemical markers using samples of whole blood obtained in a certified laboratory. . Study participants will be required to fast for 12 hours prior to the blood test. Blood collection and processing: Venous blood will be collected in the morning after a 12 hour fast with the study participant seated. Blood will be collected in tubes containing 1.5 mg/ml EDTA for procedures requiring plasma, in tubes with no additives for serum measures and citrate tubes for homeostasis endpoints. A small portion (approximately ½ teaspoon = 2.5 ml) of blood from the baseline and 6-month follow-up samples will be saved for future biomedical and molecular analysis.	during the screening/baseline visit and again during the 6-month follow-up visit.
Secondary	Thyroid Stimulating Hormone (TSH), Follicle Stimulating Hormone (FSH), Estrogen (E) and Progesterone (P4)	Measured by examining biochemical markers using samples of whole blood obtained in a certified laboratory. Study participants will be required to fast for 12 hours prior to the blood test. Blood collection and processing: Venous blood will be collected in the morning after a 12 hour fast with the study participant seated. Blood will be collected in tubes containing 1.5 mg/ml EDTA for procedures requiring plasma, in tubes with no additives for serum measures and citrate tubes for homeostasis endpoints. A small portion (approximately ½ teaspoon = 2.5 ml) of blood from the baseline and 6-month follow-up samples will be saved for future biomedical and molecular analysis.	during the screening/baseline visit and again during the 6-month follow-up visit.
Secondary	Systemic Inflammation	assessed by measuring serum pro-and-anti- inflammatory markers, which will be obtained by simple blood draw as described above and evaluated by Enzyme Linked Immunoassay (ELISA); the panel will measure pro- and anti-inflammatory factors and cytokines previously shown to be associated with metabolic disease, obesity and aging. These include: C-Reactive Protein (hs-CRP). Blood samples will then be stored at -70 degrees Celsius in a freezer at the HHWC. The blood samples will then be shipped to the Buck Institute/USF for analysis. A commercially available kit for sTNFR1 human ELISA kit (Biosource international, CA) will be utilized.	during the screening/baseline visit and again during the 6-month follow-up visit.
Secondary	Metabolic Assessments at Rest	Resting energy expenditure (REE) and Respiratory Quotient (RQ) (Day 2) will be measured at rest.Individuals are instructed to fast for 12 hours prior to the test and are instructed not to engage in vigorous physical activity for 24 hours prior to the test. Individuals will be allowed to drink water prior to the test and will rest in a recumbent position for 30 minutes prior to the start of each testing session. Metabolic measurements will be continuously taken during the test. Expired gases will be sampled and analyzed for Volume of Oxygen (VO2) and Volume of Carbon Dioxide (VCO2) concentrations by indirect calorimetry calculated via a metabolic cart (Cosmed Quark CPET, Rome, Italy) using a canopy hood set up (Cosmed Quark RMR, Rome Italy).	during the screening/baseline visit and again during the 6-month follow-up visit.
Secondary	Physical Function	Measured by the short physical performance battery as follows: The short physical performance battery is comprised of three performance measures: 1) The standing balance test requires study participants to maintain their feet in a side-by-side, semi-tandem stand, or tandem stand for 10 seconds. 2) A test of walking speed where study participants walk for 4 minutes at a normal pace; 3) The chair stand test, which evaluates lower extremity extensor muscle strength by measuring the time required for the participants to stand up and sit down from a chair five times with arms folded across the chest. Each performance measure is scored from 1-4 points (maximum 12 points). This test can be accomplished in 15 minutes.	during the screening/baseline visit and again during the 6-month follow-up visit.
Secondary	Muscular Strength	Measured by administering the hand grip test as follows: The hand-grip strength procedure of the Hand-Held Dynamometer (Baseline) will be administered to patient participants seated in a chair with a back support and fixed arm rests using a calibrated instrument. The study participants will position their thumb around one side of the instrument and their fingers along the other side of the handle. They will be instructed to squeeze the handle as long and as tightly as possible. Three measures will be recorded for each hand, alternating sides. This procedure is shown to be a valid and feasible method of assessing muscular strength in elderly adults20-21.	during the screening/baseline visit and again during the 6-month follow-up visit.
Secondary	Cardiorespiratory Fitness	Measured by a graded submaximal treadmill test using a modified Balke protocol 22. A warm-up session of approximately 5 minutes will establish comfortable walking speeds. Study participants will then walk on the treadmill for 2-minute warm-up at 0% grade, the grade of the treadmill will then be increased by 2.5% every 2 minutes until the participant can no longer continue or reaches 80% of age-predicted volume of oxygen (VO2) peak. Following the warm-up session, VO2 and carbon dioxide VCO2 production, ventilation (VE) and respiratory exchange ratio (RER) will be calculated via a metabolic cart (Cosmed Quark CPET, Rome, Italy) and a two-way non-re-breathing mask (Cosmed K2 Mask, Rome, Italy).	during the screening/baseline visit and again during the 6-month follow-up visit.
Secondary	Total Body Weight	Measured with an electronically calibrated scale (Pelstart Health-o-meter Professional 500KL) will be used to obtain the weight in kilograms of each study participant. The study participant will remove her shoes and step on the scale. The study participant will remain as still as possible. The study participant's weight in kilograms will be recorded once the digital reading is constant. The study participant will remain on the scale until the weight is recorded. The process will be repeated two additional times.; measured with an electronically calibrated scale (Pelstart Health-o-meter Professional 500KL) will be used to obtain the weight in kilograms of each study participant. The study participant will remove her shoes and step on the scale. The study participant will remain as still as possible. The study participant's weight in kilograms will be recorded once the digital reading is constant.The process will be repeated two additional times.	during the screening/baseline visit and again during the 6-month follow-up visit.
Secondary	Height	Measured with a calibrated stadiometer (Pelstart Health-o-meter Professional 500KL) will be used to obtain the height in centimeters of each study participant. The study participant will remove her shoes and step onto the floor platform facing in an outward direction with the heels together. The scapula and buttocks will remain in contact with the back of the stadiometer during the measure. The head will be positioned in a horizontal plane. The clinician will move the headboard onto the most superior aspect of the study participant's head. This procedure will be repeated two additional times. The average height in to the nearest tenth of a centimeter (0.1 cm) will be calculated on the data statistical form.	during the screening/baseline visit and again during the 6-month follow-up visit.
Secondary	Body Composition ) (lean mass, fat mass, bone density and area, central adiposity)	DEXA will be used for analysis of body composition using Hologics Horizon A DEXA. This machine is an FDA cleared-to market device. The procedure will be performed by trained technicians at the Hoskinson Health and Wellness Clinic. The study participants will be instructed to remove all metal and jewelry including their shoes before they are correctly positioned on the scan table, lying down on their back with their arms to their side. The DEXA will measure X-rays as they are transmitted through the study participant's body. The study participant will be exposed to ionizing radiation, but there is no discomfort during the measurement (0.02-0.03mR). This exposure is less than the 125mR/yr, which is the amount individuals receive from non-medical background radiation (Lunar). The low dose of radiation will not adversely affect the bone or surrounding tissue.	during the screening/baseline visit and again during the 6-month follow-up visit.
Secondary	Waist Circumference	Measured in study participants with a tape measure. The measurement of girth at the waistline provides an estimation of central adiposity17. Individuals will wear light clothing for this measurement. They are asked to stand erect and in an upright position with abdomen relaxed, arms at sides and feet together. Measures are made at the end of normal expiration at the umbilicus. The measurements are recorded to the nearest 0.1 cm. This process is repeated and the average of each of the two circumferences is used in analysis (a third measurement is obtained if the first two measurements are greater than 0.5 cm apart). Figure 1 provides a graphic representation of the measurement site for waist circumference.	during the screening/baseline visit and again during the 6-month follow-up visit.
Secondary	Cognitive Function by the Mini-Mental State Examination (MMSE)	The Mini Mental State Examination (MMSE) will be administered per standard protocol with the cut-off of 26. The MMSE is comprised of 30 questions that assesses cognitive function by evaluating attention and orientation, memory, registration, recall, calculation, language and ability to draw a complex polygon. The MMSE exhibits high levels of acceptance as a diagnostic instrument in both health care providers and researchers25. The MMSE is available in numerous language translations and can be administered in less than one hour.	during the screening/baseline visit and again during the 6-month follow-up visit.
Secondary	Executive Function (EF), Cognitive Flexibility (CF) and Mental Control (MC)	Measured by the Advanced Digital Cognitive Assessment of (BrainCheck28-29) which is a tablet-based version of six neurocognitive tests, which can be completed in 30 minutes: 1) Flanker Task, 2) Digit Symbol Substitution Test, 3) Stroop Task, 4) The Trail Making Test, 5) Balance and Coordination, 6) The Immediate and Delayed Recall Tests	during the screening/baseline visit and again during the 6-month follow-up visit.
Secondary	Depression	Measured by the Center for Epidemiologic Studies Depression Scale (CES-D Scale)30. Study participants are asked to read each question of a 20 item scale carefully, then circle one of the numbers to the right to indicate how they felt or behaved during the past week, including the assessment day. Options include: (0) Rarely or none of the time (less than 1 day), (1) Some or a little of the time (1-2 days), (2) Occasionally or a moderate amount of the time (3-4 days), (3) Most or all of the time (5-7 days). The test can be completed in approximately 10 minutes. The responses are totaled by the test administrator and the possible range of scores is between 0 to 60. Higher scores indicate the presence of more symptomatology of depression.	during the screening/baseline visit and again during the 6-month follow-up visit.
Secondary	Biological Aging	Biological Aging (Day 2) will be measured by retina scan to quantify biological aging (Welch Allyn® RetinaVue® 700 Imager) via standard clinical procedures.	during the screening/baseline visit and again during the 6-month follow-up visit.
Secondary	Phenotypic Age	Phenotypic age will be measured by blood test	during the screening/baseline visit and again during the 6-month follow-up visit.