A Placebo Controlled Trial Of L-Tryptophan In Post-Operative Delirium

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT00865202
First received: March 17, 2009
Last updated: March 27, 2013
Last verified: March 2013
  Purpose

Post-operative delirium is a common and deleterious complication in elderly patients. The investigators have previously found lower levels of serum tryptophan in post-operative elderly patients who developed delirium in comparison to post-operative elderly patients who did not develop delirium. The investigators hypothesize that post-operative supplementation of L-tryptophan will reduce the duration and incidence of post-operative delirium. This study is a double-blinded placebo controlled trial of L-tryptophan supplementation in post-operative ICU patients 60 years and older. The primary outcome measure is the comparison of duration of post-operative delirium in subjects who receive L-tryptophan supplementation versus a similar appearing control.


Condition Intervention Phase
Post-operative Delirium
Drug: L-tryptophan supplementation
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Placebo Controlled Trial Of L-Tryptophan In Post-Operative Delirium

Resource links provided by NLM:


Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • Duration of post-operative delirium [ Time Frame: post-operatively in ICU ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of post-operative delirium [ Time Frame: post-operatively in ICU ] [ Designated as safety issue: No ]

    The incidence and/or duration of excitatory (hyperactive and mixed) post-operative delirium, diagnosed by the Confusion Assessment Method-ICU (CAM-ICU) with the Richmond Agitation Sedation Score (RASS), will be reduced with enteral L-tryptophan supplementation (1 gm TID for the first 3 post-op days), compared to placebo, in older patients (≥ 60 years) undergoing operations requiring ICU admission.

    The incidence and/or duration of all types of post-operative delirium, diagnosed by the CAM-ICU with the RASS, will be reduced with enteral L-tryptophan supplementation (1 gm TID for the first 3 post-op days), compared to placebo, in older patients (≥ 60 years) undergoing operations requiring ICU admission.


  • Level of post-operative serum tryptophan [ Time Frame: post-operative day number two blood draw ] [ Designated as safety issue: No ]
  • level of post-operative serotonin and melatonin [ Time Frame: Blood draw on post-operative day number two ] [ Designated as safety issue: No ]
  • Length of post-operative ICU and hospital stay [ Time Frame: length of post-op ICU and hospital stay ] [ Designated as safety issue: No ]

Enrollment: 325
Study Start Date: December 2008
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: L-Tryptophan
L-tryptophan supplementation (1 gram enterally TID) starting post-operatively and continuing for a maximum of 9 doses or the time of discharge from ICU (whichever occurs first)
Drug: L-tryptophan supplementation
L-tryptophan 1 gram enterally TID for a maximum of nine doses or to be discontinued at the time of discharge from the ICU (whichever occurs first)
Placebo Comparator: Placebo
Similar appearing placebo administered post-operatively (1 enterally TID) for a total of nine doses or discharge from ICU (whichever occurs first)
Drug: L-tryptophan supplementation
L-tryptophan 1 gram enterally TID for a maximum of nine doses or to be discontinued at the time of discharge from the ICU (whichever occurs first)
Drug: placebo
Similar appearing placebo administered post-operatively (1 enterally TID) for a total of nine doses or discharge from ICU (whichever occurs first)

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Included subjects will be 60 years and older undergoing an operation with a planned ICU admission post-operatively.

Exclusion Criteria:

  • Medications that, when combined with tryptophan, increase the risk of serotonin syndrome. The classes of medications include:

    • monoamine oxidase inhibitors
    • selective serotonin reuptake inhibitors
    • serotonin-norepinephrine reuptake inhibitors
    • triptans
    • opioids
    • central nervous system stimulants
    • bupropion
    • St. John's Wort
  • Patients who undergo an operation on their brain.
  • Factors which prevent delirium assessment with the CAM-ICU: vision impairment or non-fluent English speakers.
  • A lowered seizure threshold including:

    • history of seizure disorder
    • alcohol abuse defined by a high AUDIT score (>8 females and >13 males)
    • benzodiazepine or barbiturate abuse within three months of the study
    • OR a positive urine toxicology screen for alcohol, benzodiazepines or barbiturates.
  • Significant liver disease (Child's class B or greater) or significant renal disease (Creatinine ≥2.0).
  • History of Huntington's or Addison's disease. (As requested by the FDA)
  • History of bipolar disorder or a psychotic disorder (such as a psychotic major depression, schizophrenia, schizoaffective disorder, or psychosis in Alzheimer's disease or other dementia). (As requested by the FDA)
  • Women who are not post-menopausal. (As requested by the FDA)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00865202

Locations
United States, Colorado
Denver Veterans Affairs Medical Center
Denver, Colorado, United States, 80220
Sponsors and Collaborators
University of Colorado, Denver
Investigators
Principal Investigator: Thomas Robinson, MD University of Colorado, Denver
  More Information

Publications:
Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT00865202     History of Changes
Other Study ID Numbers: 08-0543
Study First Received: March 17, 2009
Last Updated: March 27, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Colorado, Denver:
delirium
surgery
operation
geriatric
complication

Additional relevant MeSH terms:
Delirium
Confusion
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Tryptophan
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 15, 2014