Effectiveness of Two Types of Treatment in Restoring Muscle After Hip or Knee Surgery
Condition: Hip Fracture; Osteoarthritis; Femur Head Necrosis
MeSH terms: Femur Head Necrosis; Necrosis; Hip Fractures
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

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.
    

Intervention name(s): Essential amino acid supplement; Ketoconazole; Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 15g of essential amino acid in capsule form three times daily during hospitalization, continued through 6 weeks after discharge.; 200mg ketoconazole twice daily; started night before surgery and continued through hospitalization.; Placebo for Ketoconazole
Intervention MeSH terms: Ketoconazole
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Treatment
Keywords: Hip Replacement Arthroplasty; Hip Replacement Surgery; Hip Surgery; Hip Rehabilitation; Avascular Necrosis; Knee replacement surgery; Total knee arthroplasty