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Methylglyoxal (MGO) Lowering Cocktail to Reduce Appetite in Obese Individuals

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ClinicalTrials.gov Identifier: NCT05083546
Recruitment Status : Not yet recruiting
First Posted : October 19, 2021
Last Update Posted : October 19, 2021
Sponsor:
Information provided by (Responsible Party):
University of California, San Francisco

Brief Summary:
Mechanisms that drive addiction to sugar rich foods are a major driving factor in the pathogenesis of obesity, which has become one of the most significant health care burdens. The molecular underpinnings of these hedonic mechanisms that drive addiction to sugar are poorly understood. The investigators demonstrated that methylglyoxal (MGO) derived Advanced Glycation Endproducts (AGEs) enhance food intake especially under a high sugar diet. The investigators identified a methylglyoxal (MGO) lowering cocktail, Gly-low, a combination of alpha-lipoic acid, nicotinamide, thiamine, pyridoxamine, and piperine that demonstrates a multimodal effect influencing many pathways related to aging including calorie restriction. Glycation lowering (Gly-low) treatment significantly reduces food intake and weight gain in the db/db mice that lack the leptin receptor. The investigators also extended the lifespan of C57BL/6 mice fed with these compounds starting when they were 24 months old. Based on these results, the investigators hypothesized that methylglyoxal (MGO) lowering cocktail of compounds can be given to adults with obesity, specified as body mass index (BMI) >27, to lower serum and urinary markers of insulin resistance, lower boy mass index (BMI), and lower food intake.

Condition or disease Intervention/treatment Phase
Obesity Aging Drug: Gly-low Other: Placebo Phase 1 Phase 2

Detailed Description:

The aging population in the United States of America and around the world is expected to put enormous pressure on the medical system and thus aging remains the biggest challenge for biomedicine. The current approaches to slow aging or age-related diseases rely on targeting specific pathways for each indication, whereas the cause of aging is multifactorial. Hence, developing drugs that can function in a multimodal fashion to engage multiple pathways involved in aging is likely to be a much more effective approach.

Previous studies have demonstrated that combining mutations in the insulin and tOR (target of rapamycin) pathway can result in a nearly five-fold extension in lifespan. This study proposes to achieve similar effects pharmacologically. A compound mix has been identified utilizing glycation lowering (Gly-low) compounds that alter multiple key pathways involved in aging including the reduction of calorie intake, Nicotinamide adenine dinucleotide (NAD) metabolism, inflammation, glycation stress and increased fat burning. Preliminary findings that have shown significant increases in survival of normal and diabetic mice models fed with Gly-low confirms the efficacy of multimodal benefits of Glycation lowering (Gly-low) compounds. Glycation lowering (Gly-low) compounds were chosen based on their ability to protect neurons against glycation stress and consist of 5 compounds that have been designated GRAS (generally regarded as safe) by the Food and Drug Administration (FDA). Based on these results, the investigators hypothesize that methylglyoxal (MGO) lowering cocktail of compounds can be given to adults with obesity, specified as body mass index body mass index (BMI) >27, to lower serum and urinary markers of insulin resistance, lower body mass index (BMI), and lower food intake. Successful completion of this innovative project will result in a cocktail of compounds that can complement ongoing treatments to reduce obesity and enhance the health and slow age-related diseases.

This is a single center, double-blind, placebo-controlled, randomized trial. 100 subjects will be recruited between the ages of 50 and 70 yrs with a body mass index (BMI)>27. The participant will take 3 Gly-low supplements in pill form orally by mouth once in the morning. Baseline measurements in body mass index (BMI) (height and weight), waist circumference, food intake and dietary behavior (by questionnaire), urine, and serum will be obtained. Body mass index (BMI) will be measured every 12 weeks. The primary endpoints will be measures of physical frailty, based on performance and a clinical frailty index, and cognitive performance based on a cognitive impairment questionnaire, including memory, will be measured after 6 months and 12 months. Urine and serum will be analyzed every 12 weeks for various aging and metabolic markers. Patients will also be monitored for side effects or other compound related issues.

Screening data will be reviewed to determine subject eligibility. Subjects who meet all inclusion criteria and none of the exclusion criteria will be entered into the study.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Double-Blinded, Randomized Control Trial
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Participants will be computer sequence-randomized to receive either oral daily dosing ofthe MGO cocktail or placebo. Both participants and study team members will be blinded to treatment arm.
Primary Purpose: Treatment
Official Title: Testing the Impact of a Combination of Dietary Supplements With Multimodal Effects on Longevity Mechanisms on Reducing Body Weight and Delaying Aging
Estimated Study Start Date : April 1, 2022
Estimated Primary Completion Date : May 1, 2023
Estimated Study Completion Date : July 1, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Intervention
MGO cocktail containing a combination of alpha-lipoic acid, nicotinamide, thiamine, pyridoxamine, and piperine
Drug: Gly-low
MGO cocktail containing a combination of alpha-lipoic acid, nicotinamide, thiamine, pyridoxamine, and piperine

Placebo Comparator: Control
sugar pill
Other: Placebo
sugar pill




Primary Outcome Measures :
  1. Change in body mass index (BMI) from baseline to 1 year [ Time Frame: baseline and one year ]
    Body Mass Index (BMI) is a calculated from a person's weight in kilograms divided by the square of height in meters.

  2. Change in frailty from baseline to 1 year [ Time Frame: baseline and 1 year ]
    Frailty will be assessed and measured using a questionnaire-based method as well as analyzing the physical performance of the subject in clinic. The Clinical Frailty Scale (CFS) is a judgement-based frailty tool that evaluates specific domains including comorbidity, function, and cognition to generate a frailty score ranging from 1 (very fit) to 9 (terminally ill).

  3. Change of cognition from baseline to 1 year [ Time Frame: baseline to 1 year ]
    Cognition will be assessed and measured using a questionnaire-based method. The Clinical Frailty Scale (CFS) is a judgement-based frailty tool that evaluates specific domains including comorbidity, function, and cognition to generate a frailty score ranging from 1 (very fit) to 9 (terminally ill).


Secondary Outcome Measures :
  1. Blood Marker Glucose for Aging and Insulin Resistance [ Time Frame: baseline to 1 year ]
    Blood samples will be collected and analyzed over the course of the study to measure the blood marker glucose in mmol/L associated with aging and insulin resistance.


Other Outcome Measures:
  1. Blood Marker Insulin for Aging and Insulin Resistance [ Time Frame: baseline to 1 year ]
    Blood samples will be collected and analyzed over the course of the study to measure the blood marker insulin in ulU/mL associated with aging and insulin resistance.



Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Obese (BMI >27) individuals

Exclusion Criteria:

  • must be older than 50 years of age or older

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05083546


Contacts
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Contact: Victoria Hogue 415-302-7443 victoria.hogue@gmail.com

Locations
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United States, California
University of California, San Francisco
San Francisco, California, United States, 94143
Sponsors and Collaborators
University of California, San Francisco
Investigators
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Principal Investigator: Marshall Stoller, MD University of California, San Francisco
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Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT05083546    
Other Study ID Numbers: 20-32631
First Posted: October 19, 2021    Key Record Dates
Last Update Posted: October 19, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No IPD will be shared.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No