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

Study Overview
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Brief Summary
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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.

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

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

Conditions
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Post-operative Delirium

Intervention / Treatment
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* Drug: L-tryptophan supplementation
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: L-Tryptophan<br>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) | Drug: L-tryptophan supplementation<br>* 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)<br>* Other names: L-tryptophan 1 gm PO TID starting the evening of surgery;|
| Placebo Comparator: Placebo<br>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) | Drug: L-tryptophan supplementation<br>* 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)<br>* Other names: L-tryptophan 1 gm PO TID starting the evening of surgery;Drug: placebo<br>* Similar appearing placebo administered post-operatively (1 enterally TID) for a total of nine doses or discharge from ICU (whichever occurs first)<br>* Other names: Similar appearing placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Post-operative Delirium |  | post-operatively daily in ICU until discharged from ICU | 

Secondary Outcome Measures

| Outcome Measure | 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. | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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delirium, surgery, operation, geriatric, complication