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Novel Methodology to Measure Protein Accumulation

This study is currently recruiting participants.
Verified November 2012 by Mayo Clinic
Sponsor:
Information provided by (Responsible Party):
K. Sreekumaran Nair, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01505621
First received: January 4, 2012
Last updated: November 7, 2012
Last verified: November 2012
History of Changes
  Purpose

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.


Condition Intervention
Aging
 Other: L[ring-13C6]phenylalanine

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Novel Methodology to Measure Protein Accumulation

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Isotopic enrichment of plasma and skeletal muscle proteins achieved by oral ingestion of [13C6]-phenylalanine [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
    The abundance of post-translational modifications of plasma and muscle proteins will be measured using mass spectrometry.


Secondary Outcome Measures:
  • Assess differences in protein accumulation as a function of age [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
    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.


Biospecimen Retention:   Samples With DNA

On day one of the study (day of the study drink administration): blood samples and skeletal muscle biopsy (vastus lateralis). Muscle biopsy tissue will be frozen subsequent to collection.

Week 2 and 3 of the study: blood sample collection Week 4 of the study: blood sample and skeletal muscle (vastus lateralis) biopsy. Muscle biopsy tissue will be frozen subsequent to collection.


Estimated Enrollment: 24
Study Start Date: December 2011
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Young
Healthy adults 18-30 years old
 Other: L[ring-13C6]phenylalanine
Oral drink composed of essential amino acids including L[ring-13C6]phenylalanine
Elderly
Healthy adults greater than 65 years old
 Other: L[ring-13C6]phenylalanine
Oral drink composed of essential amino acids including L[ring-13C6]phenylalanine

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population

Two groups of otherwise healthy participants will be recruited: young (18-30 years) and old (≥65 years). We anticipate screening up to 30 individuals for each group (up to 60 total for study) in order to enroll 12 individuals for each group (24 total for study). A high ratio of screened to enrolled participants is necessary due to exclusion criteria and concern about finding healthy older participants and relatively inactive younger participants. An equal number of participants will be enrolled in each group. We will attempt to have an equal number of men and women.

Criteria

Inclusion Criteria:

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

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01505621

Locations
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Deborah Sheldon     507-255-8082     sheldon.deborah@mayo.edu    
Contact: Rozalina Grubina, MD         grubina.rozalina@mayo.edu    
Principal Investigator: K. Sreekumaran Nair, MD, PhD            
Sub-Investigator: Rozalina Grubina, MD            
Sponsors and Collaborators
Mayo Clinic
  More Information

No publications provided

Responsible Party: K. Sreekumaran Nair, Professor of Medicine, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01505621     History of Changes
Other Study ID Numbers: 11-004969
Study First Received: January 4, 2012
Last Updated: November 7, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Mayo Clinic:
Aging
Protein accumulation
Protein damage

ClinicalTrials.gov processed this record on May 16, 2013