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

Post-operative Delirium Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00865202
• Other study ID #: 08-0543
• Status: Completed
• Phase: Phase 3
• First received: March 17, 2009
• Last updated: May 26, 2017
• Start date: December 2008
• Est. completion date: December 2012

Study information

• Verified date: May 2017
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 301
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Delirium
• Post-operative Delirium

Intervention

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

Locations

Country	Name	City	State
United States	Denver Veterans Affairs Medical Center	Denver	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
University of Colorado, Denver

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Duration of Post-operative Delirium		post-operatively daily in ICU until discharged from ICU
Secondary	Incidence of Post-operative Delirium	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.	post-operatively daily in ICU until discharged from ICU
Secondary	Level of Post-operative Serum Tryptophan		post-operative day number two blood draw
Secondary	Level of Post-operative Melatonin		Blood draw on post-operative day number two
Secondary	Length of Post-operative ICU and Hospital Stay		length of post-op hospital stay