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

NCT ID: NCT00865202

Last Updated: 2017-06-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 301 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-31
• Study Completion Date: 2012-12-31

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.

Conditions

Post-operative Delirium

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

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)

Group Type: EXPERIMENTAL

L-tryptophan supplementation

Intervention Type: DRUG

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

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)

Group Type: PLACEBO_COMPARATOR

L-tryptophan supplementation

Intervention Type: DRUG

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

Intervention Type: DRUG

Similar appearing placebo administered post-operatively (1 enterally TID) for a total of nine doses or discharge from ICU (whichever occurs first)

Interventions

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)

Intervention Type: DRUG

placebo

Similar appearing placebo administered post-operatively (1 enterally TID) for a total of nine doses or discharge from ICU (whichever occurs first)

Intervention Type: DRUG

Other Intervention Names

L-tryptophan 1 gm PO TID starting the evening of surgery; Similar appearing 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)

• Minimum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thomas Robinson, MD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

Denver Veterans Affairs Medical Center

Denver, Colorado, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 18789427 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19106695 (View on PubMed)

Other Identifiers

08-0543

Identifier Type: -

Identifier Source: org_study_id