Pilot Study of GLY-LOW Supplementation in Postmenopausal Women With Obesity
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- Insulin Resistance (IR)
研究概览
简要总结
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).
详细描述
Study Population:
Healthy, postmenopausal (> 1 year from last menstrual cycle) adult females (at birth), > 55 years of age with obesity (≥ 30 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 reported. 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 syndrome with similar prevalence worldwide. Older, post-menopausal females, in particular, are at increased risk of developing central obesity due to a reduction in endogenous ovarian hormone production. 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 approach. More concerning, is the lack of rigorous, scientific evidence to support conventional dietary therapies for reducing aging-related central obesity and associated metabolic dysfunction. 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 function. 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 examined. 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 pathways. The effect of GLY-LOW supplementation on these obesity and biological age-related impairments in post-menopausal adult female humans with obesity is unknown.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 56 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Post-menopausal (>1 year from last menstrual cycle) adult females (at birth) >55 years of age with obesity (BMI ≥ 30)
排除标准
- •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.
研究组 & 干预措施
GLY-LOW supplement
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.
干预措施: GLY-LOW (Biological)
结局指标
主要结局
Insulin Resistance (IR)
时间窗: During the screening/baseline visit and again during the 6-month follow-up visit.
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.
Fasting Insulin (I) and Glucose (G)
时间窗: During the screening/baseline visit and again during the 6-month follow-up visit.
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.
BMI [weight (kg) divided by height (m2)]
时间窗: During the screening/baseline visit and again during the 6-month follow-up visit.
Total body weight and height were measured with an electronically calibrated scale and stadiometer (Pelstart Health-o-meter Professional 500KL) with participants in light, loose fitting clothing without shoes.
Glycosylated Hemoglobin [Hemoglobin A1C (HBA1C)]
时间窗: During the screening/baseline visit and again during the 6-month follow-up visit.
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.
Body Composition [lean mass, fat mass, bone density and area, central adiposity (DEXA); waist circumference]
时间窗: During the screening/baseline visit and again during the 6-month follow-up visit.
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.
次要结局
- Physical Function(During the screening/baseline visit and again during the 6-month follow-up visit.)
- Muscular Strength(During the screening/baseline visit and again during the 6-month follow-up visit.)
- Cardiorespiratory Fitness(During the screening/baseline visit and again during the 6-month follow-up visit.)
- Cognitive Function by the Mini-Mental State Examination (MMSE)(During the screening/baseline visit and again during the 6-month follow-up visit.)
- Executive Function (EF), Cognitive Flexibility (CF) and Mental Control (MC)(During the screening/baseline visit and again during the 6-month follow-up visit.)
- Self-reported Caloric Intake(During the screening/baseline visit and again during the 6-month follow-up visit.)
- Total Cholesterol, Low Density Lipoprotein (LDL), High Density Lipoprotein (HDL) and Triglycerides (TRI)(During the screening/baseline visit and again during the 6-month follow-up visit.)
- Systolic (SBP) and Diastolic Blood Pressure (DPB)(During the screening/baseline visit and again during the 6-month follow-up visit.)
- Metabolic Assessments at Rest(During the screening/baseline visit and again during the 6-month follow-up visit.)
- Thyroid Stimulating Hormone (TSH), Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), Estrogen (E) and Progesterone (P4)(During the screening/baseline visit and again during the 6-month follow-up visit.)
- Depression(During the screening/baseline visit and again during the 6-month follow-up visit.)
- Systemic Inflammation(During the screening/baseline visit and again during the 6-month follow-up visit.)
- Total Body Weight(During the screening/baseline visit and again during the 6-month follow-up visit.)
- Height(During the screening/baseline visit and again during the 6-month follow-up visit.)
- Waist Circumference(During the screening/baseline visit and again during the 6-month follow-up visit.)
- Biological Aging(During the screening/baseline visit and again during the 6-month follow-up visit.)
- Phenotypic Age(During the screening/baseline visit and again during the 6-month follow-up visit.)
研究者
Sanjay Dhar
Director of Research
Hoskinson Health and Wellness Clinic