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
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: 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 August 20, 2014