Muscle Perfusion and Protein Metabolism in Elderly

Aging Clinical Trial

Official title:

A Phase I Trial Examining Muscle Perfusion and Protein Metabolism in Elderly and Young

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00945256
• Other study ID #: 03-213
• Secondary ID: R01AG021539
• Status: Completed
• Phase: Phase 1
• First received: July 22, 2009
• Last updated: January 5, 2016
• Start date: May 2003
• Est. completion date: May 2009

Study information

• Verified date: April 2014
• Source: The University of Texas Medical Branch, Galveston
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study was to examine the role skeletal muscle perfusion plays in mediating muscle protein synthesis in healthy older and younger individuals. The investigators hypothesized that normalization of muscle perfusion in older men and women via exercise or infusion of a vasodilator would enhance nutritive flow and skeletal muscle protein synthesis in the elderly similar to that of their younger counterparts.

Description:

The purpose of this study was to examine muscle protein metabolism in healthy young and elderly subjects during pharmacologic vasodilation of the lower limb vasculature in combination with increased amino acids delivery. We obtained femoral arteriovenous blood samples and v. lateralis muscle biopsies during a primed continuous infusion of L-[ring-13C6] Phenylalanine. Muscle protein kinetics were measured in the basal state and during a 180 min infusion of sodium nitroprusside (SNP) and amino acids (Premsol 10%) (SNP+AA). Skeletal muscle microvascular recruitment and flow were measured during the basal state and SNP+AA using contrast-enhanced ultrasound (CEU).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: May 2009
• Est. primary completion date: May 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

All inclusion criteria must be fulfilled throughout the study. At enrollment, subjects must fit the following criteria:

1. Age: young 18-40 yrs; elderly 60-85 yrs.

2. Availability of transportation (i.e., subjects must be able to provide their own transportation to UTMB).

3. Ability to sign informed consent (score >24 on 30 item mini-mental status exam and no errors on assessment of judgment).

Exclusion Criteria:

None of the following exclusion criteria should be present at enrollment or throughout the study:

1. Patients with limiting or unstable angina or who demonstrate cardiac abnormalities such as > 0.2 mV horizontal or downsloping ST segment depression, frequent arrhythmias (>10 PVC/min), or valvular disease.

2. Any patient with atrial fibrillation, history of syncope, angina, or congestive heart failure.

3. Patients with vascular disease, as determined by the presence of risk factors of peripheral atherosclerosis (i.e., hypertension, obesity, uncontrolled diabetes, and evidence of venous or arterial insufficiency upon palpation of femoral, popliteal, and pedal arteries).

4. Peripheral vascular disease as determined by history or abnormal ankle-brachial index by Doppler (< 1.0).

5. Any subject with blood pressure on three consecutive measurements taken at rest on separate occasions that has a systolic pressure >170 mm Hg or a diastolic blood pressure >100 mm Hg will be excluded. Subjects will not be included if they are taking blood pressure medication and have a blood pressure above these criteria.

6. Any person HIV-seropositive, with active hepatitis, or any other immunosuppressive or autoimmune disease.

7. Any patient taking beta blockers, vasodilators, angiotensin-converting enzyme inhibitors, calcium channel blockers, or alpha blockers.

8. Any patient with uncontrolled metabolic diseases including any patient with liver or renal disease.

9. Glucose intolerance: fasting plasma glucose concentration 110-126 mg/dL (6.1-7 mmol/L) and/or 2-h plasma glucose 140-200 mg/dL (7.8-11.1 mmol/L) during oral glucose tolerance test (OGTT).

10. Currently in muscle strengthening program.

11. Total knee replacement or moderate to severe degenerative joint disease of knees.

12. Anemia (hemoglobin <13 g/dL in males or <12 g/dL in females).

13. Any history of hypo- or hyper-coagulation disorders, including patients taking Coumadin or with a history of deep venous thrombosis (DVT) or pulmonary embolism (PE) at any point in their lifetimes.

14. Currently taking aspirin and cannot stop for 7 days (i.e., medical indication for continued aspirin such as transient ischemic attacks).

15. Presence of acute illness or metabolically unstable chronic illness.

16. Heart disease requiring therapy or recent myocardial infarction (less than 1 year)

17. Currently on weight-loss diet.

18. Active cancer or in short-term remission (less than 3 years).

19. Alcohol or drug abuse.

20. History of >20 packs per year cigarette smoking.

21. Recent (within 6 months) ingestion or injection or transdermal administration of anabolic steroids, corticosteroids, estrogens, or progestagens.

22. History of falls (1 fall in the past year which required medical attention, or more than 2 falls/year regardless of severity).

23. Allergy to iodides, penicillin or shellfish.

24. Any subject with a know hypersensitivity to octafluoropropane.

25. Any subject with a cardiac shunt.

26. Any subject with chronic obstructive pulmonary disease (COPD).

Study Design

Allocation: Randomized, Intervention Model: Factorial Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Aging

Intervention

Other:
• Aerobic Exercise
45 minuties of treadmill walking was completed at 40% VO2 peak

Drug:
• Sodium Nitroprusside
Sodium Nitroprusside was given in a constant infusion for 180 minutes at a rate of 0.114 ug/kg/min

Dietary Supplement:
• Amino Acid Drink
7.5 gram Amino Acid drink

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
The University of Texas Medical Branch, Galveston	National Institute on Aging (NIA)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mixed Muscle Fractional Synthesis Rate (FSR)	The rate at which the body makes new muscle was assessed by determining the fractional synthesis rate (FSR). This technique determines how quickly new amino acids are used to make muscle. In this technique, a special (but natural and non-radioactive) version of an amino acid is infused into the blood. This special version of the amino acid is heavier than the most common version the same amino acid. This property allows it to be identified in a muscle sample. By determining how much of the special amino acid has accumulated over time in a muscle sample, the fractional synthesis rate can be determined. For example, if the rate were such that 1 of every 100 amino acids were of the special type after 1 day, the fractional synthesis rate would be 1% per day. In other words, 1/100 of the muscle would be newly made each day.	Acute ( 8 hours)	No