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

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:

MedlinePlus related topics: Delirium

Drug Information available for: Tryptophan

U.S. FDA Resources

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

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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:

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

ClinicalTrials.gov processed this record on February 27, 2015