Clinical trial NCT03263442: High Dose Intravenous Thiamine for the Prevention of Delirium in Allogeneic Hematopoietic Stem Cell Transplantation
Official title: Randomized Placebo Controlled Trial of High Dose Intravenous Thiamine for the Prevention of Delirium in Allogeneic Hematopoietic Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hematopoietic Stem Cell Transplantation
Delirium
Thiamine Deficiency
Lead sponsor: UNC Lineberger Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: Rising Tide Foundation
First posted: 2017-08-28
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Purpose: To conduct a randomized controlled pilot study investigating the use of high dose intravenous (IV) thiamine to prevent delirium and mitigate the long-term effects of delirium, including health-related quality of life (HRQOL), functional status, and neuropsychiatric outcomes, in patients admitted to University of North Carolina (UNC) Hospital for allogeneic hematopoietic stem cell transplant (HSCT).

Participants: 60 adult inpatients admitted to the UNC Bone Marrow Transplant Unit for allogeneic stem cell transplant.

Procedures (methods): Participants will be admitted for allogeneic HSCT and on the day after transplant randomized to seven days of high dose IV thiamine or placebo. Thiamine levels will be measured weekly and participants will be assessed for evidence of delirium using validated measures. Validated measures will also be used to assess cognitive function, depression, post-traumatic stress symptoms, functional status, and HRQOL prior to hospitalization and at one, three, and six months after transplant.

Detailed description: Delirium is a common and potentially preventable neuropsychiatric complication in cancer patients receiving hematopoietic stem cell transplantation (HSCT) that has profound consequences. Among cancer patients hospitalized for HSCT, delirium occurs in approximately 40% of patients and increases the risk of mortality. Long-term, delirium in this population results in worse physical health, mental health, and quality of life. Though strategies to prevent delirium have the potential to significantly improve the lives of people living with cancer, research in this area is extremely limited. Thiamine deficiency is also ubiquitous during HSCT and a known contributor to the development of delirium in other patient populations. High dose intravenous (IV) thiamine is an evidence-based and promising treatment for delirium, but no one has studied IV thiamine as a prevention strategy.

This is a randomized double-blind controlled trial in participants undergoing allogeneic HSCT to determine if high dose IV thiamine can prevent delirium and minimize the deleterious impact of delirium on health-related quality of life (HRQOL), functional status, and other neuropsychiatric outcomes. The investigators will recruit 60 patients admitted for allogeneic HSCT at UNC, randomize them to treatment with high dose IV thiamine (n = 30) versus placebo (n = 30), and systematically evaluate all participants for delirium and related comorbidities. The investigators will use the Delirium Rating Scale (DRS) to measure the severity and duration of delirium immediately prior to transplant and after HSCT until 30 days post-transplant or discharge. If delirium is identified, the DRS will be administered daily until delirium resolves. The investigators will obtain thiamine levels and other laboratory parameters associated with delirium the day after transplant, and continue to monitor thiamine levels weekly thereafter. The investigators will also monitor HRQOL, functional status, depression, post-traumatic stress symptoms, and cognitive function prior to transplant and at one, three, and six months after transplant to elucidate the persistent impact of delirium in this population and the potential for thiamine to mitigate these negative outcomes.

Eligibility criteria: Inclusion Criteria:

* Admission to the UNC Hospital Bone Marrow Transplant Unit for allogeneic stem cell transplant
* At least 18 years of age
* Able to speak English
* Able to provide informed consent

Exclusion Criteria:

* A history of adverse reaction to IV thiamine
* Pregnancy, confirmed by a negative pregnancy test within 30 days of study enrollment

Primary outcomes:
measure: Percentage of Participants With Delirium
timeFrame: Assessments will occur in the week prior to transplant, then 3 times weekly post-transplant until 30 days post-transplant or discharge, whichever comes first.
Secondary outcomes:
measure: Delirium Severity
timeFrame: Assessments will occur in the week prior to transplant (baseline), then at least 3 times post-transplant on a weekly basis until 30 days post-transplant or discharge, whichever comes first, up to week 5
measure: Delirium Duration
timeFrame: Assessments will occur in the week prior to transplant, then 3 times weekly post-transplant until 30 days post-transplant or discharge, whichever comes first.
measure: Concentration of Thiamine Status Stratified by Delirium Status
timeFrame: From end of 7-day intervention period until the development of delirium at any point during the post-transplant hospitalization up to a maximum of 30 days
measure: Change in Health-related Quality of Life Scores (Month 1)
timeFrame: From baseline to one month post-transplant
measure: Change in Health-related Quality of Life Scores (Month 3)
timeFrame: Baseline to three months post-transplant
measure: Change in Health-related Quality of Life Scores (Month 6)
timeFrame: Baseline to six months post-transplant
measure: Change in Depression Scores (Month 1)
timeFrame: Baseline to one month post-transplant
measure: Change in Depression Scores (Month 3)
timeFrame: Baseline to three months post-transplant
measure: Change in Depression Scores (Month 6)
timeFrame: Baseline to six months post-transplant
measure: Change in Post-traumatic Stress Symptom Scores (Month 1)
timeFrame: Baseline to one month post-transplant
measure: Change in Post-traumatic Stress Symptom Scores (Month 3)
timeFrame: Baseline to three months post-transplant
measure: Change in Post-traumatic Stress Symptom Scores (Month 6)
timeFrame: Baseline to six months post-transplant
measure: Change in Cognitive Function Scores (Month 1)
timeFrame: From baseline to one month post-transplant
measure: Change in Cognitive Function Scores (Month 3)
timeFrame: Baseline to three months post-transplant
measure: Change in Cognitive Function Scores (Month 6)
timeFrame: From baseline to six months post-transplant
measure: Change in Functional Status Scores (Month 1)
timeFrame: Baseline to one month post-transplant
measure: Change in Functional Status Scores (Month 3)
timeFrame: From baseline to three months post-transplant
measure: Change in Functional Status Scores (Month 6)
timeFrame: Baseline to six months post-transplant
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Donald Rosenstein, MD
role: STUDY_CHAIR
affiliation: University of North Carolina, Chapel Hill
name: Zev Nakamura, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nakamura ZM, Deal AM, Park EM, Quillen LJ, Chien SA, Stanton KE, McCabe SD, Heiling HM, Wood WA, Shea TC, Rosenstein DL. A randomized double-blind placebo-controlled trial of intravenous thiamine for prevention of delirium following allogeneic hematopoietic stem cell transplantation. J Psychosom Res. 2021 Jul;146:110503. doi: 10.1016/j.jpsychores.2021.110503. Epub 2021 Apr 27.