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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.
The sudy will compare rates and duration of postoperative delirium in groups that receive L-tryptophan supplementation compared to placebo.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| L-Tryptophan | Experimental | 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) |
|
| Placebo | Placebo Comparator | 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) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| L-tryptophan supplementation | 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Duration of Post-operative Delirium | post-operatively daily in ICU until discharged from ICU |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
Medications that, when combined with tryptophan, increase the risk of serotonin syndrome. The classes of medications include:
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:
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)
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| Name | Affiliation | Role |
|---|---|---|
| Thomas Robinson, MD | University of Colorado, Denver | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Denver Veterans Affairs Medical Center | Denver | Colorado | 80220 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18789427 | Background | 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. | |
| 19106695 | Background | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Study Drug | L-tryptophan 1 gm enterally TID starting the evening of the operation |
| FG001 | Placebo | Similar appearing placebo |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
301 total study participants
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| ID | Title | Description |
|---|---|---|
| BG000 | L-tryptophan | L-tryptophan 1 gm enterally TID starting the evening of the operation |
| BG001 | Placebo | similar appearing placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Duration of Post-operative Delirium | Posted | Mean | Standard Deviation | days | post-operatively daily in ICU until discharged from ICU |
|
|
Postoperative Nausea
Postoperative Nausea
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Study Drug | L-tryptophan 1 gm enterally TID starting the evening of the operation |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Thomas Robinson MD | University of Colorado | 303-724-2728 | thomas.robinson@ucdenver.edu |
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| ID | Term |
|---|---|
| D000071257 | Emergence Delirium |
| D003693 | Delirium |
| ID | Term |
|---|---|
| D003221 | Confusion |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
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|
| placebo | Drug | Similar appearing placebo administered post-operatively (1 enterally TID) for a total of nine doses or discharge from ICU (whichever occurs first) |
|
|
| post-operatively daily in ICU until discharged from ICU |
| Level of Post-operative Serum Tryptophan | post-operative day number two blood draw |
| Level of Post-operative Melatonin | Blood draw on post-operative day number two |
| Length of Post-operative ICU and Hospital Stay | length of post-op hospital stay |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
| 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. | Posted | Number | percentage of patient escitatorydelirium | post-operatively daily in ICU until discharged from ICU |
|
|
|
| Secondary | Level of Post-operative Serum Tryptophan | Posted | Mean | Standard Deviation | umol/L | post-operative day number two blood draw |
|
|
|
| Secondary | Level of Post-operative Melatonin | Posted | Mean | Standard Deviation | pg/mL | Blood draw on post-operative day number two |
|
|
|
| Secondary | Length of Post-operative ICU and Hospital Stay | Posted | Mean | Standard Deviation | days | length of post-op hospital stay |
|
|
|
| 0 |
| 152 |
| 0 |
| 152 |
| EG001 | Placebo | Similar appearing placebo | 0 | 149 | 0 | 149 |
The manuscript has been accepted by the Journal of the American Geriatrics Society for publication.
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012816 | Signs and Symptoms |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |