Clinical trial NCT00865202: A Placebo Controlled Trial Of L-Tryptophan In Post-Operative Delirium
Official title: A Placebo Controlled Trial Of L-Tryptophan In Post-Operative Delirium
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Post-operative Delirium
Keywords: delirium
surgery
operation
geriatric
complication
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2009-03-19
Enrollment: 301
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility 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)

Primary outcomes:
measure: Duration of Post-operative Delirium
timeFrame: post-operatively daily in ICU until discharged from ICU
Secondary outcomes:
measure: Incidence of Post-operative Delirium
timeFrame: post-operatively daily in ICU until discharged from ICU
measure: Level of Post-operative Serum Tryptophan
timeFrame: post-operative day number two blood draw
measure: Level of Post-operative Melatonin
timeFrame: Blood draw on post-operative day number two
measure: Length of Post-operative ICU and Hospital Stay
timeFrame: length of post-op hospital stay
Other outcomes:
Locations:
city: Denver
country: United States
facility: Denver Veterans Affairs Medical Center
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Thomas Robinson, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.