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

NCT05083546 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: 20-32631
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Obesity; Aging

Outcome Measures

Primary Outcomes (3)

• Change in body mass index (BMI) from baseline to 1 year

  Body Mass Index (BMI) is a calculated from a person's weight in kilograms divided by the square of height in meters.

  baseline and one year

• Change in frailty from baseline to 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).

  baseline and 1 year

• Change of cognition from 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).

  baseline to 1 year

Secondary Outcomes (1)

• Blood Marker Glucose for Aging and Insulin Resistance

  baseline to 1 year

Other Outcomes (1)

• Blood Marker Insulin for Aging and Insulin Resistance

  baseline to 1 year

Study Arms (2)

Intervention

EXPERIMENTAL

MGO cocktail containing a combination of alpha-lipoic acid, nicotinamide, thiamine, pyridoxamine, and piperine

Drug: Gly-low

Control

PLACEBO COMPARATOR

sugar pill

Other: Placebo

Interventions

Gly-low DRUG

MGO cocktail containing a combination of alpha-lipoic acid, nicotinamide, thiamine, pyridoxamine, and piperine

Intervention

Placebo OTHER

sugar pill

Control

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Obese (BMI \>27) individuals

You may not qualify if:

• must be older than 50 years of age or older

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Obesity

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Marshall Stoller, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double-Blinded, Randomized Control Trial

Study Record Dates

• First Submitted: July 26, 2021
• First Posted: October 19, 2021
• Study Start: December 1, 2024
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: August 29, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)