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

Primary Purpose

Post-operative Delirium

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
L-tryptophan supplementation
placebo
Sponsored by
University of Colorado, Denver
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Post-operative Delirium focused on measuring delirium, surgery, operation, geriatric, complication

Eligibility Criteria

60 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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)

Sites / Locations

  • Denver Veterans Affairs Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

L-Tryptophan

Placebo

Arm 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)

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)

Outcomes

Primary Outcome Measures

Duration of Post-operative Delirium

Secondary Outcome Measures

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.
Level of Post-operative Serum Tryptophan
Level of Post-operative Melatonin
Length of Post-operative ICU and Hospital Stay

Full Information

First Posted
March 17, 2009
Last Updated
May 26, 2017
Sponsor
University of Colorado, Denver
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1. Study Identification

Unique Protocol Identification Number
NCT00865202
Brief Title
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

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
December 2008 (undefined)
Primary Completion Date
December 2012 (Actual)
Study Completion Date
December 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Colorado, Denver

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Post-operative Delirium
Keywords
delirium, surgery, operation, geriatric, complication

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
301 (Actual)

8. Arms, Groups, and Interventions

Arm Title
L-Tryptophan
Arm Type
Experimental
Arm 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)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm 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)
Intervention Type
Drug
Intervention Name(s)
L-tryptophan supplementation
Other Intervention Name(s)
L-tryptophan 1 gm PO TID starting the evening of surgery
Intervention Description
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
Intervention Name(s)
placebo
Other Intervention Name(s)
Similar appearing placebo
Intervention Description
Similar appearing placebo administered post-operatively (1 enterally TID) for a total of nine doses or discharge from ICU (whichever occurs first)
Primary Outcome Measure Information:
Title
Duration of Post-operative Delirium
Time Frame
post-operatively daily in ICU until discharged from ICU
Secondary Outcome Measure Information:
Title
Incidence of Post-operative Delirium
Description
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.
Time Frame
post-operatively daily in ICU until discharged from ICU
Title
Level of Post-operative Serum Tryptophan
Time Frame
post-operative day number two blood draw
Title
Level of Post-operative Melatonin
Time Frame
Blood draw on post-operative day number two
Title
Length of Post-operative ICU and Hospital Stay
Time Frame
length of post-op hospital stay

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas Robinson, MD
Organizational Affiliation
University of Colorado, Denver
Official's Role
Principal Investigator
Facility Information:
Facility Name
Denver Veterans Affairs Medical Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80220
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
18789427
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.
Results Reference
background
PubMed Identifier
19106695
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.
Results Reference
background

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

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