Adjuvant Nutrition for Critically Ill Trauma Patients
Condition: Trauma
MeSH terms: Wounds and Injuries
Study type: Interventional
Phase: Phase 1

Summary: 
      Of the four million trauma cases each year that will require hospitalization, 200,000 will be
      classified as severe trauma. During the hospital stay, malnutrition is a major complication
      in about 50% of the patient population. The result is muscle wasting which is a major risk
      factor for increased morbidity and mortality. In this study we postulate that supplementation
      with beta-hydroxy-beta-methylbutyrate (HMB), arginine and glutamine (HMB/Arg/Gln)or HMB alone
      to these severely traumatized patients can stem the loss of muscle tissue and whole body
      nitrogen and in turn decrease morbidity and mortality. This hypothesis is based on two recent
      studies showing the same nutritional mixture of HMB/Arg/Gln can reverse the muscle wasting
      associated with AIDS and Cancer. The hypermetabolic state seen in AIDS and cancer have a
      similar multifactorial etiology as seen in trauma. There is an increase in the mobilization
      of fat and muscle, increased or normal metabolic rate, increased protein breakdown, and an
      increased or normal glucose turnover. In addition, HMB alone has been shown to reduce
      nitrogen loss, decrease muscle proteolysis and muscle damage within the first 48 hours to
      three weeks after initiating supplementation during a strenuous exercise program. Male and
      female patients (n=100) will be recruited at the time of admittance to the Trauma ICU with an
      ISS of greater than 18. Patients who meet the inclusion/exclusion criteria will be randomized
      to receive either 1) standard tube feed plus HMB/Arg/Gln, 2) standard tube feed plus HMB
      alone, or 3)standard tube feed (control) in a double-blinded fashion. Clinical outcomes
      measures will be assessed through out the hospital stay and on an outpatient basis at weeks 4
      and 12. Muscle proteolysis and nitrogen economy will be evaluated on daily basis while in the
      hospital and after 4 weeks on an out patient basis. If as expected, Phase I results confirm
      the effectiveness of the nutrient mixture in trauma patients, expanded multicenter studies
      will be proposed in Phase II.
    

Detailed description: 
      OBJECTIVES:

      To compare the effectiveness of immediate nutritional intervention with either HMB, arginine,
      and glutamine or HMB alone with that of a placebo supplement in critically ill trauma
      patients on:

        -  decreasing muscle protein turnover and nitrogen loss

        -  improving nutritional status,

        -  improving clinical outcomes,

        -  preventing total body weight and skeletal muscle loss and

        -  improving immune status

      OUTLINE:

      This is a double blind, placebo-controlled randomized clinical study. After receiving
      informed consent for participation in the study from the next of kin, patients will be
      randomly assigned to one of the 3 treatment arms:

      Arm 1: Standard tube feed plus a nutritional supplement supplying 3 grams of HMB, 14 grams of
      arginine and 14 grams of glutamine per day. The supplement will be divided into two equal
      dosages with one dose being given in the morning and one dose given in the evening.

      Arm 2: Standard tube feed plus a nutritional supplement supplying 3 grams of HMB. This
      nutritional supplement will contain gelatin and non-essential amino acids to be
      isonitrogenous with the supplement in Arm 1. The supplement will also be divided into two
      equal dosages with one dose being given in the morning and one dose given in the evening.

      Arm 3: Standard tube feed plus a nutritional supplement supplying a mixture of gelatin and
      amino acids to be isonitrogenous with the supplement in Arm 1. The supplement will again be
      divided into two equal dosages with one dose being given in the morning and one dose given in
      the evening.

      Patients will receive the nutritional supplements for a period of 4 weeks. If a patient
      leaves the hospital or ICU before that time and/or discontinues the enteral nutrition
      support, the supplements will be continued orally for the full 4-week period.

      Several clinical outcome measures will be followed such as hospital length of stay, ICU
      length of stay, mortality, number of ventilator days, and incidence of infectious
      complications. Clinical outcomes will be assessed during the hospital stay and at 4 and 12
      weeks. Muscle protein metabolism will be measured during the hospital stay and at 4 weeks.
      Nutritional status while hospitalized will be assessed by serum pre-albumin levels on days
      0,1, 3, 7, and 14. White blood count, number of confirmed infections and C-Reactive Protein
      levels will serve as proxies for immune status.
    

Intervention name(s): Juven (nutritional), HMB (nutritional)
Intervention type(s): Procedure
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Treatment