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

Official Title: “A Placebo Controlled Trial Of L-Tryptophan In Post-Operative Delirium”

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.

Intervention(s) in this Clinical Trial

• 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)

Arms, Groups and Cohorts in this Clinical Trial

• 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)
• 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)

Primary Measures

• Duration of post-operative delirium
  • Time Frame: post-operatively in ICU
    Safety Issue?: No

Secondary Measures

• Incidence of post-operative delirium
  • Time Frame: post-operatively in ICU
    Safety Issue?: No
• Level of post-operative serum tryptophan
  • Time Frame: post-operative day number two blood draw
    Safety Issue?: No
• level of post-operative serotonin and melatonin
  • Time Frame: Blood draw on post-operative day number two
    Safety Issue?: No
• Length of post-operative ICU and hospital stay
  • Time Frame: length of post-op ICU and hospital stay
    Safety Issue?: No

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
• opiods
• 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)

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 60 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: University of Colorado, Denver Other

Overall Clinical Trial Officials and Contacts

Overall Contact: Thomas Robinson, MD 303-724-2728 thomas.robinson@ucdenver.edu

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00865202

Study ID Number: COMIRB 08-0543

ClinicalTrials.gov Identifier: NCT00865202

Health Authority: United States: Food and Drug Administration