Effectiveness of Two Types of Treatment in Restoring Muscle After Hip or Knee Surgery

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Arkansas
ClinicalTrials.gov Identifier:
NCT00393848
First received: October 27, 2006
Last updated: May 30, 2014
Last verified: May 2014
  Purpose

The purpose of this study is to determine the effects of two postoperative interventions designed to preserve muscle protein after major hip or knee surgery.


Condition Intervention Phase
Hip Fracture
Osteoarthritis
Femur Head Necrosis
Drug: Essential amino acid supplement
Drug: Ketoconazole
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
Official Title: Restoration of Muscle Following Hip Surgery

Resource links provided by NLM:


Further study details as provided by University of Arkansas:

Primary Outcome Measures:
  • Muscle Protein Synthesis [ Time Frame: Perioperative and discharge ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in Maximal Voluntary Contraction [ Time Frame: Baseline and 6 weeks post surgery ] [ Designated as safety issue: No ]

Enrollment: 40
Study Start Date: October 2006
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Experiment 2 - Experimental Group Drug: Ketoconazole
200mg ketoconazole twice daily; started night before surgery and continued through hospitalization.
No Intervention: Experiment 1 - Standard of care Group
Experimental: Experiment 1 - Experimental Group Drug: Essential amino acid supplement
15g of essential amino acid in capsule form three times daily during hospitalization, continued through 6 weeks after discharge.
Placebo Comparator: Experiment 2 - Placebo Group Drug: Placebo
Placebo for Ketoconazole

Detailed Description:

Hip fractures among the elderly are a major health concern. Nearly one-third of elderly hip fracture patients die within 1 year of the injury. Events surrounding the actual injury and any necessary surgical repair often lead to reduced muscle protein, and eventually, muscle strength. Loss in everyday function and independence may follow, especially in elderly or frail individuals. The decrease in protein synthesis may be caused by two main events following injury and surgery: prolonged inactivity and an increase in stress hormone levels. Preventing a loss in protein may help to improve outcomes for individuals undergoing hip surgery and rehabilitation. The purpose of this study is to determine the effects of two postoperative interventions designed to retain muscle protein after major hip or knee surgery in adults.

This study will include two experiments. Experiment 1 will include individuals who are scheduled for hip or knee replacement surgery because of osteoarthritis (the need to repair or replace the affected joint), or avascular necrosis (bone tissue death caused by lack of blood supply). Experiment 1 participants will be randomly assigned to one of two groups:

  • Group 1 participants will receive daily supplements of essential amino acids, which are thought to stimulate protein synthesis.
  • Group 2 participants will receive standard rehabilitation care while in the hospital and will serve as controls for the effect of time on recovery.

Participants will be in the hospital for about 4 days. On the morning of surgery, blood and urine collection will occur. During surgery, substances called tracers, measuring the extent of protein synthesis and breakdown, will be injected into a vein for the first metabolic study. Additional blood and muscle samples will also be taken. After surgery, when participants arrive in the surgical recovery unit and are able to eat, they will begin to record all food intake and will receive their assigned treatment. Treatment, in the form of gel capsules, will be taken 2.5 hours after each meal. Urine will be collected throughout hospitalization and blood will be collected each morning. Prior to discharge, a 24-hour metabolic study will be performed, including tracer injections and muscle biopsies. After discharge, participants will be provided with 6 weeks' worth of their assigned treatment. Follow-up visits will occur 2 and ~6 to 8 weeks after surgery. These visits will include various muscle function and physical performance tests. Participants will also undergo a dual energy x-ray absorptiometry (DEXA) scan, which will be used to determine muscle mass.

Experiment 2 participants will include individuals scheduled for either hip or knee replacement surgery or fracture repair surgery. Participants will be randomly assigned to one of two groups:

  • Group 1 participants will receive the antifungal drug ketoconazole, which is thought to reduce levels of the stress hormone cortisol.
  • Group 2 participants will receive placebo and standard rehabilitation care while in the hospital.

Participants will begin taking their assigned treatments the day prior to surgery; those with a hip fracture will take their assigned treatment at least 4 hours prior to surgery. The same procedures that occurred in Experiment 1 during surgery and hospitalization will be carried out during Experiment 2. The second metabolic study, however, will last only 1 hour and will include a standard clinical meal.

  Eligibility

Ages Eligible for Study:   30 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria for All Participants:

  • Scheduled for surgery because of osteoarthritis, avascular necrosis, fracture, or revision of total joint replacement in the hip or knee

Exclusion Criteria for All Participants:

  • Taking insulin, thiazolidinediones (TZD), or metformin
  • Kidney insufficiency, as indicated by serum creatinine of more than 2.0 mg/dl
  • Recently treated cancer other than basal cell carcinoma
  • Any other condition or event that would be considered as reason for exclusion by the study investigators
  • Pregnancy

Exclusion Criteria for Experiment 1 Participants:

  • Severe hypertension as indicated by requiring more than two drugs for blood pressure control
  • History of hypo- or hypercoagulation disorders, including individuals who have taken warfarin (Coumadin)
  • Atrial fibrillation, angina, or congestive heart failure

Exclusion Criteria for Experiment 2 Participants:

  • Liver disease or abnormal liver function tests
  • HIV infected
  • Active hepatitis
  • Any uncontrolled metabolic disease, including liver or kidney disease
  • Taking medications that use the cytochrome P450 pathway for metabolism and unable to discontinue their use for the duration of the study
  • Require certain medications. More information on this criterion can be found in the protocol.
  • Gastrointestinal absorption disorders that affect nutrient uptake
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00393848

Locations
United States, Arkansas
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
Sponsors and Collaborators
University of Arkansas
Investigators
Principal Investigator: Arny Ferrando, PhD University of Arkansas
  More Information

No publications provided

Responsible Party: University of Arkansas
ClinicalTrials.gov Identifier: NCT00393848     History of Changes
Other Study ID Numbers: R01 AR052293, 70451, 1R01AR052293-01A2
Study First Received: October 27, 2006
Results First Received: January 6, 2014
Last Updated: May 30, 2014
Health Authority: United States: Federal Government

Keywords provided by University of Arkansas:
Hip Replacement Arthroplasty
Hip Replacement Surgery
Hip Surgery
Hip Rehabilitation
Avascular Necrosis
Knee replacement surgery
Total knee arthroplasty

Additional relevant MeSH terms:
Osteoarthritis
Hip Fractures
Necrosis
Femur Head Necrosis
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Femoral Fractures
Fractures, Bone
Wounds and Injuries
Hip Injuries
Leg Injuries
Pathologic Processes
Osteonecrosis
Bone Diseases
Ketoconazole
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014