Investigating the Link Between Advanced Glycation End Products (AGEs) and Muscle Wasting in Sarcobesity

NCT06438900 | Recruiting DMC

• 1 other identifier: CE049/2024
• Study Type: observational
• Target: 195
• Locations: 1 country
• Sites: 1

Brief Summary

The study aims to explore whether a high level of AGEs (Advanced Glycation end products) derived from the diet may mediate diet-related muscle loss in Western-type diet, influencing the onset and progression of sarcopenia, predisposing to earlier and more severe metabolic consequences, including type 2 diabetes (T2D). The primary objective of the study is to investigate how the accumulation of AGEs is correlated with muscle loss in adult patients with obesity and type 2 diabetes or lipodystrophy in order to identify possible targets to mitigate the metabolic alterations caused by the Western diet (WD). Specifically, circulating AGEs levels on the skin will be evaluated and correlated with the stage of sarcopenia in a group of patients with obesity and a T2D diagnosis. Furthermore, the relationship between disease duration and AGE levels will be assessed. A secondary objective will be to analyze the clinical data obtained to identify metabolites and metabolic pathways responsible for the phenotype induced by the WD. The ultimate aim of the study is therefore to verify whether high levels of AGEs are correlated with an early and/or more pronounced onset of sarcopenia, concurrently with an increase in inflammation and oxidative stress.

Conditions

Sarcopenia; Obesity

Keywords

Advanced glycation end products; Sarcobesity; Obesity; Sarcopenic

Outcome Measures

Primary Outcomes (6)

• Skeletal mass functionality for sarcopenia definition

  Functional parameters of skeletal muscle defined by muscle strength measured through hand grip strength (HGS) The test requires the patient to tighten the handle the dynamometer with the maximum possible force, then maintaining the contraction for at least 5 seconds; you should repeat the test on the other hand (it is normal that the dominant expresses a higher force) and possibly repeat the test 2-3 times, with a break between different attempts, then going to calculate the average oh the kg moved with the dynamometer

  evaluation of sarcopenia state through study completion, an average of 1 year

• Skeletall mass fuctionality for sarcopenia definition

  Functional parameters of skeletal muscle defined by the chair test: five-times sit-to-stand test; time duration 30-second chair stand test. You measure by considering the ability in seconds to get up and sit down from the chair properly

  evaluation of sarcopenia state through study completion, an average of 1 year

• Skeletall mass calculation for sarcopenia definition

  The percentage of skeletal muscle mass relative to body mass will be considered. Skeletal mass will be calculated as follows: SM(Kg)=\[(h\^2/(BIA resistance)0.401)+(gender3.825)+(age\*0.071)\]+5.102 Where h indicates height measured in cm, gender is a dichotomous variable taking a value of 1 for males and 0 for females, and age is measured in years. From this measurement, the percentage of skeletal muscle mass (%SMM) will be calculated: %SMM=(SM (Kg))/(Body mass (Kg))\*100

  evaluation of sarcopenia state through study completion, an average of 1 year

• Number of participants with sarcopenia

  According to consensus statement of European Society for Clinical Nutrition and Metabolism (ESPEN) and dell' European Association for the Study of Obesity (EASO) guidelines, individuals with altered skeletal muscle functionality parameters (HGS \< 16 kg for females and \< 27 kg for males or chair test \>15 seconds for both males and females \[27\]), altered %BF(body fat) (≥ 25% for males and ≥35% for females \[28\]), and altered %SMM (\<35.6% (≤28.7% severe sarcopenia) for males, \<28.4% (≤23% severe sarcopenia) for females) will be defined as sarcopenic.

  evaluation of sarcopenia state through study completion, an average of 1 year

• Advanced glycation end products quantification

  AGE levels will be measured using skin fluorescence, using the "AGE reader mu" device (range from 1.3 to 5 level of AGEs respect to the patient's age).

  evaluation of AGEs through study completion, an average of 1 year

• Endogenous and exogenous AGEs plasma quantification

  AGEs will also be assessed at the plasma level in free form (ELISA, fluorescence assay) or bound to hemoglobin (HbA1c clinical practice test), both measured in pg/mL

  evaluation of AGEs through study completion, an average of 1 year

Secondary Outcomes (9)

• With questionnaires assessment of socio-demographic characteristics

  evaluation of socio-demographic characteristics through study completion, an average of 1 year

• Anthropometric measurements

  evaluation of weight and body composition through study completion, an average of 1 year

• Anthropometric measurements

  evaluation of height through study completion, an average of 1 year

• Anthropometric measurements

  evaluation of BMI (body mass index) through study completion, an average of 1 year

• Anthropometric measurements

  evaluation of circumferences through study completion, an average of 1 year

Eligibility Criteria

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

Study Population

Given a type I error rate (α) of 0.05 and a power of 80%, 195 subjects will be needed to observe a significant correlation between AGE levels and sarcobesity indices of at least 0.2. Considering the low prevalence of lipodystrophy and a recruitment duration of one year, approximately 35 subjects with this condition are expected to be included. The remaining 160 subjects will have diabetes and obesity. Furthermore, considering that the duration of diabetes may influence AGE levels and sarcobesity, both subjects with long-standing diabetes (80 patients) and those with less than one year of diagnosis (80 patients) will be selected, which can be considered comparable to subjects in pre-diabetes.

You may qualify if:

• Patients of both sexes.
• Adults.
• BMI compatible with obesity and a diagnosis of type 2 diabetes under good metabolic control (HbA1c \< 7.5%) within 15 years of entry into the study or diagnosis of lipodystrophy (included in the European Consortium of Lipodystrophies (ECLip) Registry (eclip-web.org))

You may not qualify if:

• Age under 18 years.
• Secondary obesity or genetic diseases (Prader-Willi Syndrome, Down Syndrome); metabolic and endocrine disorders (Cushing's syndrome, hypothyroidism).
• Subjects with: Inflammatory Bowel Disease (IBD), cancer.
• Confirmed or planned pregnancy during the study participation months.

Sponsors & Collaborators

• Azienda Ospedaliero Universitaria Maggiore della Carita: lead

Study Sites (1)

SCDU Endocrinology, AOU Ospedale Maggiore della Carità

Novara, 28100, Italy

RECRUITING

Related Publications (23)

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MeSH Terms

Conditions

Sarcopenia; Obesity

Condition Hierarchy (Ancestors)

Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight

Study Officials

• Flavia Prodam, MD PhD

  AOU Maggiore della Carità di Novara

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Flavia Prodam, MD PhD

CONTACT

+39-0321-660693; flavia.prodam@med.uniupo.it

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 14, 2024
• First Posted: June 3, 2024
• Study Start: June 15, 2024
• Primary Completion (Estimated): May 15, 2026
• Study Completion (Estimated): May 15, 2026
• Last Updated: August 1, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)