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

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.

Condition or disease	Intervention/treatment	Phase
Post-operative Delirium	Drug: L-tryptophan supplementation; Drug: placebo	Phase 3

Detailed Description:

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

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	301 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Prevention
Official Title:	A Placebo Controlled Trial Of L-Tryptophan In Post-Operative Delirium
Study Start Date :	December 2008
Actual Primary Completion Date :	December 2012
Actual Study Completion Date :	December 2012

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Experimental: L-Tryptophan; 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)	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); Other Name: L-tryptophan 1 gm PO TID starting the evening of surgery
Placebo Comparator: 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)	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); Other Name: L-tryptophan 1 gm PO TID starting the evening of surgery Drug: placebo; Similar appearing placebo administered post-operatively (1 enterally TID) for a total of nine doses or discharge from ICU (whichever occurs first); Other Name: Similar appearing placebo

Outcome Measures

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Primary Outcome Measures :

1. Duration of Post-operative Delirium [ Time Frame: post-operatively daily in ICU until discharged from ICU ]

Secondary Outcome Measures :

1. Incidence of Post-operative Delirium [ Time Frame: 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.

2. Level of Post-operative Serum Tryptophan [ Time Frame: post-operative day number two blood draw ]
3. Level of Post-operative Melatonin [ Time Frame: Blood draw on post-operative day number two ]
4. Length of Post-operative ICU and Hospital Stay [ Time Frame: length of post-op hospital stay ]

Eligibility Criteria

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Ages Eligible for Study:	60 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
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

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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

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications:

Robinson TN, Raeburn CD, Angles EM, Moss M. Low tryptophan levels are associated with postoperative delirium in the elderly. Am J Surg. 2008 Nov;196(5):670-4. doi: 10.1016/j.amjsurg.2008.07.007. Epub 2008 Sep 11.

Robinson TN, Raeburn CD, Tran ZV, Angles EM, Brenner LA, Moss M. Postoperative delirium in the elderly: risk factors and outcomes. Ann Surg. 2009 Jan;249(1):173-8. doi: 10.1097/SLA.0b013e31818e4776.

Responsible Party:	University of Colorado, Denver
ClinicalTrials.gov Identifier:	NCT00865202 History of Changes
Other Study ID Numbers:	08-0543
First Posted:	March 19, 2009
Results First Posted:	June 1, 2017
Last Update Posted:	June 1, 2017
Last Verified:	May 2017

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	Neurocognitive Disorders; Mental Disorders; Tryptophan; Antidepressive Agents, Second-Generation; Antidepressive Agents; Psychotropic Drugs