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

Phase 3

Completed

• Conditions: Post-operative Delirium
• Interventions: Drug: L-tryptophan supplementation; Drug: placebo

• Registration Number: NCT00865202
• Lead Sponsor: University of Colorado, Denver

Brief Summary

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.

Detailed Description

The sudy will compare rates and duration of postoperative delirium in groups that receive L-tryptophan supplementation compared to placebo.

Study Timeline

• Study Start: 2008-12
• Study First Submitted: 2009-03-17
• Study First Submitted QC: 2009-03-18
• Study First Posted: 2009-03-19
• Primary Completion: 2012-12
• Study Completion: 2012-12
• Results First Submitted: 2014-05-27
• Status Verified: 2017-05
• Results First Submitted QC: 2017-05-26
• Last Update Submitted: 2017-05-26
• Results First Posted: 2017-06-01
• Last Update Posted: 2017-06-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 301

Inclusion Criteria

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

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
L-Tryptophan	L-tryptophan supplementation	L-tryptophan supplementation (1 gram enterally three times per day) starting post-operatively and continuing for a maximum of 9 doses or the time of discharge from ICU (whichever occurs first)
Placebo	L-tryptophan supplementation	Similar appearing placebo administered post-operatively (1 enterally three times per day) for a total of nine doses or discharge from ICU (whichever occurs first)
Placebo	placebo	Similar appearing placebo administered post-operatively (1 enterally three times per day) for a total of nine doses or discharge from ICU (whichever occurs first)

Primary Outcome Measures

Name	Time	Method
Duration of Post-operative Delirium	post-operatively daily in ICU until discharged from ICU

Secondary Outcome Measures

Name	Time	Method
Incidence of Post-operative Delirium	post-operatively daily in ICU until discharged from ICU	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	post-operative day number two blood draw
Level of Post-operative Melatonin	Blood draw on post-operative day number two
Length of Post-operative ICU and Hospital Stay	length of post-op hospital stay

Trial Locations

Locations (1)

Denver Veterans Affairs Medical Center; 🇺🇸 Denver, Colorado, United States