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

University of Colorado Denver (CU Denver)

Status and phase: Completed; Phase 3

Conditions: Post-operative Delirium

Treatments: Drug: placebo; Drug: L-tryptophan supplementation

Study type: Interventional

Funder types: Other

Identifiers

NCT00865202

08-0543

Details and patient eligibility

About

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.

Full description

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

Enrollment: 301 patients

Sex: All

Ages: 60+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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301 participants in 2 patient groups, including a placebo group

L-Tryptophan

Experimental group

Description:

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)

Treatment:

Drug: L-tryptophan supplementation

Placebo

Placebo Comparator group

Description:

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)

Treatment:

Drug: L-tryptophan supplementation

Drug: placebo