Clinical trial NCT06813261: GLYLO Supplement Pilot Trial on Glycation and Aging in Postmenopausal Women
Official title: A Randomized, Placebo-Controlled, Double-Blind, Parallel-Group Pilot Trial Investigating the Impact of a Glycation Lowering (GLYLO) Supplement on Geroscience Outcomes in Postmenopausal Women
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Postmenopause
Metabolism
Geroscience
Keywords: Dietary supplement
Healthy aging
Women's health
Hormones
Advanced glycation end products (AGEs)
Glycation stress
Metabolic stress
Lead sponsor: Buck Institute for Research on Aging
Sponsor class: OTHER
First posted: 2025-02-06
Enrollment: 30
Sex: FEMALE
Minimum age (years): 45
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The aim of this study is to assess the effectiveness of GLYLO, a dietary supplement, in postmenopausal women aged 45 to 65 who are overweight or obese and have elevated HbA1c levels. Specifically, the study seeks to evaluate whether GLYLO can reduce advanced glycation end products (AGEs) levels, which are harmful compounds formed when sugar attaches to proteins or fats in the body and can contribute to aging and disease. The primary outcome of the study is to determine if GLYLO reduces AGEs, enhances metabolic and hormonal health, and mitigates age-related functional decline.

This study includes one screening visit and three testing visits over a 6-month period. After eligibility is confirmed, participants will be randomly assigned to one of two groups to take either GLYLO (two capsules daily) or a placebo at home for 24 weeks. Participants will provide blood samples at every visit. During the three testing visits, they will complete physical performance and cognitive function tests, provide both blood and urine samples, and fill out quality of life and 24-hour dietary intake questionnaires. The dietary intake questionnaires will be completed only twice i.e. at the baseline visit and again at the final 6-month visit.

Detailed description: Telephone Screening: Subjects are screened for eligibility by telephone for major exclusion criteria. They then attend a screening visit. Eligible participants will receive an Informed Consent Form to review prior to the in-person screening visit.

Pre-Visit Requirements for all Visits: Fasting (water only) ≥10 hours, no alcohol, exercise, or cannabis products ≥10 hours.

Visit 1: Screening Visit

Upon arrival, participants will provide written consent before study procedures. A fasting blood sample will be collected for blood chemistry, hematology, lipid profile, HbA1c, and thyroid panel analysis. Participants will undergo measurements of height, weight, BMI, vital signs (blood pressure, heart rate, body temperature), and menopausal status. Medical history, current medications/supplements, and inclusion/exclusion criteria will be recorded. Eligibility will be confirmed within 2 weeks following a review by medical officers.

Visit 2: Baseline Visit Participants will undergo assessments of weight, waist/hip circumference, BMI, body composition (BIA), and vital signs. A fasting blood sample will be drawn for blood chemistry, hematology, lipids, HbA1c, and hormone panels (FSH, LH, E2, progesterone, testosterone). Additional blood will be stored for future analysis (MGO, AGEs, metabolomics, inflammation, phenotypic age). Participants will provide a midstream urine sample for archiving.

Physical Tests: Short Physical Performance Battery (SPPB), 6-minute walk test, handgrip strength.

Cognitive Tests: Montreal Cognitive Assessment (MoCA), Digit Symbol Substitution Task, Trails A \& B.

Functional Tests: Skin autofluorescence (AGE Reader, DiagnOptics), Pulse Wave Velocity (PWV), retinal imaging.

Quality of life questionnaires: Pittsburgh Sleep Quality Index (PSQI), European Quality of Life 5 Dimensions (EQ-5D-5L).

Participants will receive GLYLO capsules for 12 weeks and instructions for use. They will also be provided with access to the Automated Self-administered 24-hour Dietary Assessment Tool (ASA24) and a wearable actigraphy device (Fitbit) to track activity.

At-Home Procedures Participants will take one capsule of GLYLO per day after their first meal for the first week, and two capsules per day from Week 2 onwards (after the first and last meals). They will complete a daily Study Log for 14 days, tracking product intake and symptoms. From Day 15, an abbreviated version will be used. Compliance will be monitored through telephonic interviews at Weeks 2, 4, 6, 8, 10, 14, 18, and 22. ASA24 diet logs will be completed during Weeks 1 and 23.

Visit 3: Interim Visit (3-Month Visit) Participants will return unused products and complete all assessments from the Baseline Visit. Compliance will be reviewed, and participants will receive GLYLO for an additional 12 weeks and a new Study Log.

Visit 4: Final Visit (6-Month Visit) Participants will return unused products and repeat all assessments from the Baseline and Interim Visits. They will not receive additional study products at this visit. Participants will be asked to guess the treatment they received to assess blinding.

Eligibility criteria: Inclusion Criteria:

1. Adults identified as female at birth with ovaries present (self-report)
2. Post menopause \>1y since last menses (self-report)
3. Aged 45 - 65 y
4. BMI ≥ 27 (screening measurement). Participants may weigh themselves at home for two days and share with the study team if their weight at the screening visit results in them being slightly under the BMI cut-off.
5. HbA1c 5.7- 6.4% (screening measurement)
6. Able to read and speak English well enough to provide informed consent and understand instructions.
7. Able to attend in-person visits at The Buck Institute

Exclusion Criteria:

1. Not identified as female at birth (self-report)
2. Surgical menopause (self-report)
3. Hysterectomy and/or ovariectomy (self-report)
4. Receiving hormone replacement therapy (HRT) (self-report).
5. Currently prescribed or received weight loss medications within the past 6 months, or currently enrolled in a defined weight loss program. Weight must be stable (\> 4%) within the last 3 months.
6. Regular use of GLYLO, or regular use of a supplement containing any of the ingredients in GLYLO, within the last 3 months.
7. Diabetes, T1DM or T2DM (self-report and screening tests): Treatment with any hypoglycemic agents (self-report), fasting glucose \>125 mg/dL (screening test; may reassess once), current use of hypoglycemic drugs for non-diabetic reasons (self-report).
8. Elevated blood pressure readings (screening test): Resting Systolic Blood Pressure (SBP) ≥150 mmHg or resting Diastolic Blood Pressure (DBP) ≥90 mmHg. Participants may provide home readings for two days if they do not meet this criterion at the screening visit.
9. Psychotropic and/or other medications known to significantly impact weight unless on a stable dose for ≥ 6 months (self-report).
10. Liver enzyme tests (alanine transaminase, aspartate transaminase) (screening test): \>2 times the laboratory upper limit of normal. Reassessment during screening may be allowed under some conditions (e.g., recent use of acetaminophen).
11. Immunosuppressive disorders, taking immunosuppressive medications (including oral prednisone \>10mg/day and biological immunosuppressants), or receiving chemotherapy.
12. Active gastrointestinal bleeding, or active bleeding diathesis (or resolved within 6 months prior to randomization) (self-report)
13. Active peptic ulcer disease (or resolved within 6 months prior to randomization) (self-report)
14. Active malignancy (or resolved within 6 months prior to randomization), except non-melanoma skin cancer not undergoing treatment (self-report).
15. Active infection (or resolved within 1 month prior to randomization) (self-report)
16. Allergy or hypersensitivity to any component of the supplement (self-report)
17. History of hyperthyroidism or current use of thyroid hormones (self-report), current abnormal thyroid function (blood test at screening).
18. Cognitive status: Unable to provide informed consent to participate in and safely complete the protocol, as based on the judgment of the investigators (screening visit)
19. Psychiatric status: any condition that might affect the ability to comply with the protocol in the opinion of the Clinical Investigator or Medical Officer (screening visit)
20. Active eating disorders (self-report).
21. Active diagnosis of Gout (self-report)
22. Any change to prescription medications within 3 months prior to randomization that are judged by the study physician to impact the results of the study (self-report)
23. No overnight hospitalization within 1 month prior to randomization (self-report)
24. The presence of a condition or abnormality that in the opinion of the Investigator or Medical Officer would compromise the safety of the patient or the quality of the data

Primary outcomes:
measure: Methylglyoxal (MGO)
timeFrame: Baseline, Week 12, Week 24
measure: Advance glycation end products (AGE)
timeFrame: Baseline, Week 12, Week 24
Secondary outcomes:
measure: Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)
timeFrame: Baseline, Week 12, Week 24
measure: HbA1c
timeFrame: Baseline, Week 12, Week 24
measure: Body fat
timeFrame: Baseline, Week 12, Week 24
measure: Body mass index (BMI)
timeFrame: Baseline, Week 12, Week 24
measure: Hip circumference
timeFrame: Baseline, Week 12, Week 24
measure: Follicle-stimulating hormone (FSH)
timeFrame: Baseline, Week 12, Week 24
measure: Muscle mass
timeFrame: Baseline, Week 12, Week 24
measure: Waist circumference
timeFrame: Baseline, Week 12, Week 24
Other outcomes:
measure: Retinal age
timeFrame: Baseline, Week 12, Week 24
measure: Pulse wave velocity (PWV)
timeFrame: Baseline, Week 12, Week 24
measure: Skin autofluorescence for measuring AGEs
timeFrame: Baseline, Week 12, Week 24
measure: Metabolomic analysis
timeFrame: Baseline, Week 12, Week 24
measure: Short Physical Performance Battery (SPPB)
timeFrame: Baseline, Week 12, Week 24
measure: Hand Grip Strength
timeFrame: Baseline, Week 12, Week 24
measure: Montreal Cognitive Assessment (MOCA)
timeFrame: Baseline, Week 12, Week 24
measure: Trailmaking task
timeFrame: Baseline, Week 12, Week 24
measure: Pittsburg Sleep Quality Index (PSQI)
timeFrame: Baseline, Week 12, Week 24
measure: Quality of Life Questionnaire (EQ-5D-5L)
timeFrame: Baseline, Week 12, Week 24
measure: Ovarian hormones
timeFrame: Baseline, Week 12, Week 24
measure: Concentration of inflammatory proteins
timeFrame: Baseline, Week 12, Week 24
measure: Phenotypic age
timeFrame: Baseline, Week 12, Week 24
Locations:
city: Novato
country: United States
facility: The Buck Institute for Research on Aging
state: California
Study officials:
References:
citation: Yang DH, Chiang TI, Chang IC, Lin FH, Wei CC, Cheng YW. Increased levels of circulating advanced glycation end-products in menopausal women with osteoporosis. Int J Med Sci. 2014 Mar 13;11(5):453-60. doi: 10.7150/ijms.8172. eCollection 2014.
citation: Merhi Z. Advanced glycation end-products: pathway of potentially significant pathophysiological and therapeutic relevance for metabolic syndrome in menopausal women. J Clin Endocrinol Metab. 2014 Apr;99(4):1146-8. doi: 10.1210/jc.2013-4465. Epub 2014 Feb 3. No abstract available.
citation: Chaudhuri J, Bains Y, Guha S, Kahn A, Hall D, Bose N, Gugliucci A, Kapahi P. The Role of Advanced Glycation End Products in Aging and Metabolic Diseases: Bridging Association and Causality. Cell Metab. 2018 Sep 4;28(3):337-352. doi: 10.1016/j.cmet.2018.08.014.