Novel Methodology to Measure Protein Accumulation

Completed

• Conditions: Aging
• Interventions: Other: L[ring-13C6]phenylalanine

• Registration Number: NCT01505621
• Lead Sponsor: Mayo Clinic

Brief Summary

Accumulation of damaged proteins is thought to underlie many degenerative conditions, including aging, diabetes, Alzheimer's disease, cataracts, and others. Over time, proteins can be irreversibly damaged by a variety of factors, such as reactive oxygen species, and without timely degradation they can accumulate and aggregate. We believe this can contribute to the development of chronic degenerative disorders.

The purpose of this study is to develop a novel methodology for measuring protein accumulation and test it in two groups of people: young (18-30 years) and old (≥65 years). This methodology will require that people drink a solution of essential amino acids that includes isotopically labeled L\[ring-13C6\]phenylalanine. We will then collect blood and muscle samples, to isolate plasma and skeletal muscle proteins. Participants will return to the study center four more times on a weekly interval.

We hypothesize that older proteins, which persisted in circulation and accumulated over time, will have a higher degree of post-translational oxidative damage than newly synthesized proteins.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-12
• Study First Submitted: 2012-01-04
• Study First Submitted QC: 2012-01-04
• Study First Posted: 2012-01-06
• Primary Completion: 2013-08
• Study Completion: 2013-08
• Status Verified: 2014-04
• Last Update Submitted: 2014-04-09
• Last Update Posted: 2014-04-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

• Age 18-30 years
• Age greater than 65 years

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Exclusion Criteria

• Active or uncontrolled cardiovascular disease
• Chronic kidney disease with serum creatinine ≥ 1.4 mg/dL for women and ≥ 1.5 mg/dL for men
• Chronic liver disease (elevation in serum transaminases ≥ 3 times the upper limit of normal)
• Any debilitating chronic illness, including malignancy
• Significant malabsorptive state, including prior gastric bypass surgery or inflammatory bowel disease
• Diabetes mellitus (types 1 or 2) or glucose ≥ 110 mg/dL.
• Obesity (BMI ≥ 31 kg/m2)
• Anticoagulant therapy (warfarin or heparin) or bleeding disorder that increases risk of bleeding during a muscle biopsy.
• Anemia (hemoglobin ≤ 11 g/dL)
• Use of medications known to modulate protein synthesis, mitochondrial function, and/or glucose homeostasis (including β-blockers and corticosteroids).
• Participation in another study where the 13CPhe was administered during the past 6 months.
• Moderate or high level of structured exercise (on average, ≥ 30 minutes per day and ≥ 2 days per week)
• Pregnancy
• Daily use of tobacco products (smoking or chewing); or smoking ≥7 cigarettes per week, on average. Abstinence from tobacco for ≥3 months is required before enrollment in the study.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Young	L[ring-13C6]phenylalanine	Healthy adults 18-30 years old
Elderly	L[ring-13C6]phenylalanine	Healthy adults greater than 65 years old

Primary Outcome Measures

Name	Time	Method
Isotopic enrichment of plasma and skeletal muscle proteins achieved by oral ingestion of [13C6]-phenylalanine	3 weeks	Administration of an oral amino acid mixture containing isotopically-labeled \[13C6\]-phenylalanine (13C-Phe) will result in 13C-Phe incorporation into newly synthesized proteins. Measuring isotopic enrichment (IE) of 13C-Phe immediately after administration and weekly for 3 consecutive weeks will allow for estimation of protein accumulation.
Degree of post-translational modifications in plasma and muscle proteins	3 weeks	The abundance of post-translational modifications of plasma and muscle proteins will be measured using mass spectrometry.

Secondary Outcome Measures

Name	Time	Method
Assess differences in protein accumulation as a function of age	3 weeks	Use the newly developed methodology to assess whether otherwise healthy older adults (≥65 years old) have greater accumulation of plasma and muscle proteins compared to healthy young adults (18-30 years old).
Assess differences in protein modification/damage as a function of age	3 weeks	The abundance of post-translational modification/damage of plasma and muscle proteins will be measured using mass spectrometry in young (18-30 years old)and older (\>65 years old) adults.

Trial Locations

Locations (1)

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States