High Dose Intravenous Thiamine for the Prevention of Delirium in Allogeneic Hematopoietic Stem Cell Transplantation

• Sponsor: UNC Lineberger Comprehensive Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT03263442
• Collaborator: Rising Tide Foundation (Other)
• Enrollment: 66
• Location: 1
• Arms: 2
• Actual Duration (Months): 33.8
• Patients Per Site Per Month: 2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hematopoietic Stem Cell Transplantation; Delirium; Thiamine Deficiency	Drug: Thiamine; Drug: Normal saline	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 66 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Randomized Placebo Controlled Trial of High Dose Intravenous Thiamine for the Prevention of Delirium in Allogeneic Hematopoietic Stem Cell Transplantation
• Actual Study Start Date: Oct 16, 2017
• Actual Primary Completion Date: Mar 2, 2020
• Actual Study Completion Date: Aug 10, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intervention Thiamine 200 mg IV	Drug: Thiamine; 200 mg IV three times daily for seven days; Other Names: Thiamine Hydrochloride Injection
Placebo Comparator: Control Normal saline IV	Drug: Normal saline; Normal saline IV three times daily for seven days; Other Names: Placebo

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Delirium [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.]

   Delirium incidence will be measured using the Delirium Rating Scale (DRS). The DRS is a is a 10-item, clinician-rated scale that rates the severity of delirium symptoms over a 24-hour period using all available information from the patient interview, mental status examination, medical history and tests, nursing observations, and family reports. The maximum possible score is 32. Higher scores suggest more severe symptoms. A cut-off score of > 12 has been suggested to distinguish patients with delirium from patients with other neuropsychiatric disorders. Delirium incidence will be defined as at least one assessment with DRS > 12.

Secondary Outcome Measures

1. Delirium Severity [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]

   Delirium severity will be measured using the Delirium Rating Scale (DRS). The DRS is a is a 10-item, clinician-rated scale that rates the severity of delirium symptoms over a 24-hour period using all available information from the patient interview, mental status examination, medical history and tests, nursing observations, and family reports. The score ranges from 0 to 32 with higher scores reflecting more severe symptoms. A cut-off score of > 12 has been suggested to distinguish patients with delirium from patients with other neuropsychiatric disorders. The DRS medians and ranges are reported for each group at baseline and in each week of hospitalization for thiamine and placebo groups.

2. Delirium Duration [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.]

   Delirium duration will be measured using the Delirium Rating Scale (DRS). The DRS is a is a 10-item, clinician-rated scale that rates the severity of delirium symptoms over a 24-hour period using all available information from the patient interview, mental status examination, medical history and tests, nursing observations, and family reports. The maximum possible score is 32. Higher scores suggest more severe symptoms. A cut-off score of > 12 has been suggested to distinguish patients with delirium from patients with other neuropsychiatric disorders. Delirium duration will be reported as number of consecutive days during which DRS > 12.

3. Concentration of Thiamine Status Stratified by Delirium Status [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]

   The relationship between thiamine levels at the end of the seven day administration of thiamine and the development of delirium at any point during the thirty days post-transplant or the post-transplant hospitalization, whichever comes first, will be examined. Thiamine levels (nmol/L) are presented in participants who did and did not experience delirium.

4. Change in Health-related Quality of Life Scores (Month 1) [From baseline to one month post-transplant]

   HRQOL will be assessed using the Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT). The FACT-BMT is a 47-item self-administered assessment which asks individuals to rate questions related to physical, social/family, emotional, and functional well-being on a 5-point Likert Scale (0, not at all to 4, very much). Scores are summed across the items, resulting in a score from 0 to 148, with higher scores indicating better quality of life. Negative change scores indicate worse HRQOL with time.

5. Change in Health-related Quality of Life Scores (Month 3) [Baseline to three months post-transplant]

   HRQOL will be assessed using the Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT). The FACT-BMT is a 47-item self-administered assessment which asks individuals to rate questions related to physical, social/family, emotional, and functional well-being on a 5-point Likert Scale (0, not at all to 4, very much). Scores are summed across the items, resulting in a score from 0 to 148, with higher scores indicating better quality of life. Negative change scores indicate worse HRQOL with time.

6. Change in Health-related Quality of Life Scores (Month 6) [Baseline to six months post-transplant]

   HRQOL will be assessed using the Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT). The FACT-BMT is a 47-item self-administered assessment which asks individuals to rate questions related to physical, social/family, emotional, and functional well-being on a 5-point Likert Scale (0, not at all to 4, very much). Scores are summed across the items, resulting in a score from 0 to 148, with higher scores indicating better quality of life. Negative change scores indicate worse HRQOL with time.

7. Change in Depression Scores (Month 1) [Baseline to one month post-transplant]

   Depression will be assessed using the Patient Reported Outcomes Measurement Information System - Depression (PROMIS-D) 8a short form. Scores for all PROMIS measures are reported on the T-score metric in which the mean=50 and standard deviation (SD) = 10 are centered on the general population means. Higher scores represent greater degrees of mood symptoms. Positive change scores indicate worse mood over time.

8. Change in Depression Scores (Month 3) [Baseline to three months post-transplant]

   Depression will be assessed using the Patient Reported Outcomes Measurement Information System - Depression (PROMIS-D) 8a short form. Scores for all PROMIS measures are reported on the T-score metric in which the mean=50 and standard deviation (SD) = 10 are centered on the general population means. Higher scores represent greater degrees of mood symptoms. Positive change scores indicate worse mood over time.

9. Change in Depression Scores (Month 6) [Baseline to six months post-transplant]

   Depression will be assessed using the Patient Reported Outcomes Measurement Information System - Depression (PROMIS-D) 8a short form. Scores for all PROMIS measures are reported on the T-score metric in which the mean=50 and standard deviation (SD) = 10 are centered on the general population means. Higher scores represent greater degrees of mood symptoms. Positive change scores indicate worse mood over time.

10. Change in Post-traumatic Stress Symptom Scores (Month 1) [Baseline to one month post-transplant]

    Post-traumatic stress symptoms will be measured using the Post Traumatic Stress Syndrome Scale 14 (PTSS-14). The PTSS-14 is a 14-item self-administered assessment. Questions are on a 7-point Likert-type Scale (1, never to 7, always) resulting in a total score between 14 and 98. Higher scores represent a more likely diagnosis of post-traumatic stress disorder (PTSD). Positive change scores indicate worse post-traumatic stress over time.

11. Change in Post-traumatic Stress Symptom Scores (Month 3) [Baseline to three months post-transplant]

    Post-traumatic stress symptoms will be measured using the Post Traumatic Stress Syndrome Scale 14 (PTSS-14). The PTSS-14 is a 14-item self-administered assessment. Questions are on a 7-point Likert-type Scale (1, never to 7, always) resulting in a total score between 14 and 98. Higher scores represent a more likely diagnosis of post-traumatic stress disorder (PTSD). Positive change scores indicate worse post-traumatic stress over time.

12. Change in Post-traumatic Stress Symptom Scores (Month 6) [Baseline to six months post-transplant]

    Post-traumatic stress symptoms will be measured using the Post Traumatic Stress Syndrome Scale 14 (PTSS-14). The PTSS-14 is a 14-item self-administered assessment. Questions are on a 7-point Likert-type Scale (1, never to 7, always) resulting in a total score between 14 and 98. Higher scores represent a more likely diagnosis of post-traumatic stress disorder (PTSD). Positive change scores indicate worse post-traumatic stress over time.

13. Change in Cognitive Function Scores (Month 1) [From baseline to one month post-transplant]

    Cognitive function will be assessed using the Montreal Cognitive Assessment (MOCA). The MOCA is a clinician-administered tool with scores ranging from 0 to 30. Lower scores indicate worse cognitive function. Scores ≤ 25 are considered clinically significant. Positive change scores indicate better function with time.

14. Change in Cognitive Function Scores (Month 3) [Baseline to three months post-transplant]

    Cognitive function will be assessed using the Montreal Cognitive Assessment (MOCA). The MOCA is a clinician-administered tool with scores ranging from 0 to 30. Lower scores indicate worse cognitive function. Scores ≤ 25 are considered clinically significant. Positive change scores indicate better function with time.

15. Change in Cognitive Function Scores (Month 6) [From baseline to six months post-transplant]

    Cognitive function will be assessed using the Montreal Cognitive Assessment (MOCA). The MOCA is a clinician-administered tool with scores ranging from 0 to 30. Lower scores indicate worse cognitive function. Scores ≤ 25 are considered clinically significant. Positive change scores indicate better function with time.

16. Change in Functional Status Scores (Month 1) [Baseline to one month post-transplant]

    Functional status will be measured using the Eastern Cooperative Oncology Group (ECOG) performance scale. ECOG performance status is a single question scored on a 6-point scale (range 0 to 5) with higher scores representing greater physical restriction due to illness. Negative change scores indicate better function with time.

17. Change in Functional Status Scores (Month 3) [From baseline to three months post-transplant]

    Functional status will be measured using the Eastern Cooperative Oncology Group (ECOG) performance scale. ECOG performance status is a single question scored on a 6-point scale (range 0 to 5) with higher scores representing greater physical restriction due to illness. Negative change scores indicate better function with time.

18. Change in Functional Status Scores (Month 6) [Baseline to six months post-transplant]

    Functional status will be measured using the Eastern Cooperative Oncology Group (ECOG) performance scale. ECOG performance status is a single question scored on a 6-point scale (range 0 to 5) with higher scores representing greater physical restriction due to illness. Negative change scores indicate better function with time.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27514

Sponsors and Collaborators

• UNC Lineberger Comprehensive Cancer Center
• Rising Tide Foundation

Investigators

• Study Chair: Donald Rosenstein, MD, University of North Carolina, Chapel Hill
• Principal Investigator: Zev Nakamura, MD, University of North Carolina, Chapel Hill

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 26, 2020

More Information

Publications

None provided.

• Responsible Party: UNC Lineberger Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT03263442
• Other Study ID Numbers: LCCC1726; CCR-17-300
• First Posted: Aug 28, 2017
• Last Update Posted: Oct 19, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Delirium; Thiamine Deficiency; Beriberi; Thiamine

Study Results

Participant Flow

Recruitment Details	Participants were recruited from the UNC Bone Marrow Transplant and Cellular Therapies Unit from October 2017 through February 2020.
Pre-assignment Detail	Of the 66 participants who enrolled in the study, 2 withdrew prior to randomization.

Arm/Group Title	Intervention	Control
Arm/Group Description	Thiamine 200 mg IV Thiamine: 200 mg IV three times daily for seven days	Normal saline IV Normal saline: Normal saline IV three times daily for seven days
Period Title: Inpatient Phase
STARTED	30	34
COMPLETED	28	33
NOT COMPLETED	2	1
Period Title: Inpatient Phase
STARTED	28	33
COMPLETED	27	33
NOT COMPLETED	1	0
Period Title: Inpatient Phase
STARTED	27	33
COMPLETED	26	30
NOT COMPLETED	1	3
Period Title: Inpatient Phase
STARTED	26	30
COMPLETED	24	28
NOT COMPLETED	2	2

Baseline Characteristics

Arm/Group Title	Intervention	Control	Total
Arm/Group Description	Thiamine 200 mg IV Thiamine: 200 mg IV three times daily for seven days	Normal saline IV Normal saline: Normal saline IV three times daily for seven days	Total of all reporting groups
Overall Participants	28	33	61
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.9 (12.5)	53.6 (14.7)	54.2 (13.6)
Sex: Female, Male (Count of Participants)
Female	11 39.3%	13 39.4%	24 39.3%
Male	17 60.7%	20 60.6%	37 60.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 3.6%	1 3%	2 3.3%
Not Hispanic or Latino	27 96.4%	32 97%	59 96.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	3 10.7%	6 18.2%	9 14.8%
White	25 89.3%	27 81.8%	52 85.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	28 100%	33 100%	61 100%
Education (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	14.7 (2.7)	15.3 (2.7)	15.0 (2.7)
Diagnosis (Count of Participants)
Acute leukemia	18 64.3%	19 57.6%	37 60.7%
Chronic leukemia	2 7.1%	5 15.2%	7 11.5%
Lymphoma	0 0%	2 6.1%	2 3.3%
Myelodysplastic Syndrome	5 17.9%	5 15.2%	10 16.4%
Myeloproliferative Disorder	2 7.1%	1 3%	3 4.9%
Other	1 3.6%	1 3%	2 3.3%
CIBMTR Disease Risk Index (Count of Participants)
N/A	3 10.7%	3 9.1%	6 9.8%
low	17 60.7%	19 57.6%	36 59%
intermediate	3 10.7%	9 27.3%	12 19.7%
high	5 17.9%	2 6.1%	7 11.5%
Donor Type (Count of Participants)
Matched Related Donor	9 32.1%	10 30.3%	19 31.1%
Matched Unrelated Donor	16 57.1%	18 54.5%	34 55.7%
Haploidentical	3 10.7%	5 15.2%	8 13.1%
Conditioning Regimen (Count of Participants)
Myeloablative	15 53.6%	13 39.4%	28 45.9%
Reduced Intensity or Non-Myeloablative	13 46.4%	20 60.6%	33 54.1%
ECOG Score (Count of Participants)
0	13 46.4%	18 54.5%	31 50.8%
1	15 53.6%	14 42.4%	29 47.5%
2	0 0%	1 3%	1 1.6%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Delirium
Description	Delirium incidence will be measured using the Delirium Rating Scale (DRS). The DRS is a is a 10-item, clinician-rated scale that rates the severity of delirium symptoms over a 24-hour period using all available information from the patient interview, mental status examination, medical history and tests, nursing observations, and family reports. The maximum possible score is 32. Higher scores suggest more severe symptoms. A cut-off score of > 12 has been suggested to distinguish patients with delirium from patients with other neuropsychiatric disorders. Delirium incidence will be defined as at least one assessment with DRS > 12.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

The analysis population was defined a priori as those participants who: 1.) received at least 17 of 21 (80%) scheduled study drug doses; 2.) received at least one dose on each of the study drug administration days; and 3.) had no fewer than one DRS assessment per week until they were found to be delirious, reached 30 days post-transplant, or were discharged.

Arm/Group Title	Intervention	Control
Arm/Group Description	Thiamine 200 mg IV Thiamine: 200 mg IV three times daily for seven days	Normal saline IV Normal saline: Normal saline IV three times daily for seven days
Measure Participants	28	33
Number [percentage of participants]	25 89.3%	21 63.6%

2. Secondary Outcome

Title	Delirium Severity
Description	Delirium severity will be measured using the Delirium Rating Scale (DRS). The DRS is a is a 10-item, clinician-rated scale that rates the severity of delirium symptoms over a 24-hour period using all available information from the patient interview, mental status examination, medical history and tests, nursing observations, and family reports. The score ranges from 0 to 32 with higher scores reflecting more severe symptoms. A cut-off score of > 12 has been suggested to distinguish patients with delirium from patients with other neuropsychiatric disorders. The DRS medians and ranges are reported for each group at baseline and in each week of hospitalization for thiamine and placebo groups.
Time Frame	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

Outcome Measure Data

Analysis Population Description

Attrition over time is due to hospital discharge (primary reason), withdrawal, or death.

Arm/Group Title	Intervention	Control
Arm/Group Description	Thiamine 200 mg IV Thiamine: 200 mg IV three times daily for seven days	Normal saline IV Normal saline: Normal saline IV three times daily for seven days
Measure Participants	28	33
Baseline	4.0	4.0
Week 1	4.83	4.67
Week 2	6.50	5.33
Week 3	6.33	5.17
Week 4	5.50	6.00
Week 5	20.00	7.50

3. Secondary Outcome

Title	Delirium Duration
Description	Delirium duration will be measured using the Delirium Rating Scale (DRS). The DRS is a is a 10-item, clinician-rated scale that rates the severity of delirium symptoms over a 24-hour period using all available information from the patient interview, mental status examination, medical history and tests, nursing observations, and family reports. The maximum possible score is 32. Higher scores suggest more severe symptoms. A cut-off score of > 12 has been suggested to distinguish patients with delirium from patients with other neuropsychiatric disorders. Delirium duration will be reported as number of consecutive days during which DRS > 12.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

These analyses are exclusive to those participants who experienced delirium.

Arm/Group Title	Intervention	Control
Arm/Group Description	Thiamine 200 mg IV Thiamine: 200 mg IV three times daily for seven days	Normal saline IV Normal saline: Normal saline IV three times daily for seven days
Measure Participants	7	7
Mean (Standard Deviation) [days]	2.0 (1.2)	4.4 (4.7)

4. Secondary Outcome

Title	Concentration of Thiamine Status Stratified by Delirium Status
Description	The relationship between thiamine levels at the end of the seven day administration of thiamine and the development of delirium at any point during the thirty days post-transplant or the post-transplant hospitalization, whichever comes first, will be examined. Thiamine levels (nmol/L) are presented in participants who did and did not experience delirium.
Time Frame	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

Outcome Measure Data

Analysis Population Description

Only those participants in whom thiamine levels were obtained at the end of the seven day administration were included.

Arm/Group Title	Delirium	No Delirium
Arm/Group Description	Participants who experienced delirium, defined as at least one DRS score >12, during the post-transplant hospitalization.	Participants who did not meet criteria for delirium during the post-transplant hospitalization.
Measure Participants	14	45
Mean (Standard Deviation) [nmol/L]	115.6 (69.3)	93.8 (28.5)

5. Secondary Outcome

Title	Change in Health-related Quality of Life Scores (Month 1)
Description	HRQOL will be assessed using the Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT). The FACT-BMT is a 47-item self-administered assessment which asks individuals to rate questions related to physical, social/family, emotional, and functional well-being on a 5-point Likert Scale (0, not at all to 4, very much). Scores are summed across the items, resulting in a score from 0 to 148, with higher scores indicating better quality of life. Negative change scores indicate worse HRQOL with time.
Time Frame	From baseline to one month post-transplant

Outcome Measure Data

Analysis Population Description

Participants who completed the 1 month follow-up period.

Arm/Group Title	Intervention	Control
Arm/Group Description	Thiamine 200 mg IV Thiamine: 200 mg IV three times daily for seven days	Normal saline IV Normal saline: Normal saline IV three times daily for seven days
Measure Participants	27	33
Mean (Standard Deviation) [score on a scale]	-7.53 (11.66)	-5.69 (11.59)

6. Secondary Outcome

Title	Change in Health-related Quality of Life Scores (Month 3)
Description	HRQOL will be assessed using the Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT). The FACT-BMT is a 47-item self-administered assessment which asks individuals to rate questions related to physical, social/family, emotional, and functional well-being on a 5-point Likert Scale (0, not at all to 4, very much). Scores are summed across the items, resulting in a score from 0 to 148, with higher scores indicating better quality of life. Negative change scores indicate worse HRQOL with time.
Time Frame	Baseline to three months post-transplant

Outcome Measure Data

Analysis Population Description

Participants who completed the 3 month follow-up period

Arm/Group Title	Intervention	Control
Arm/Group Description	Thiamine 200 mg IV Thiamine: 200 mg IV three times daily for seven days	Normal saline IV Normal saline: Normal saline IV three times daily for seven days
Measure Participants	26	30
Mean (Standard Deviation) [score on a scale]	-3.96 (9.11)	-1.43 (16.79)

7. Secondary Outcome

Title	Change in Health-related Quality of Life Scores (Month 6)
Description	HRQOL will be assessed using the Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT). The FACT-BMT is a 47-item self-administered assessment which asks individuals to rate questions related to physical, social/family, emotional, and functional well-being on a 5-point Likert Scale (0, not at all to 4, very much). Scores are summed across the items, resulting in a score from 0 to 148, with higher scores indicating better quality of life. Negative change scores indicate worse HRQOL with time.
Time Frame	Baseline to six months post-transplant

Outcome Measure Data

Analysis Population Description

Participants who completed the 6 month follow-up period

Arm/Group Title	Intervention	Control
Arm/Group Description	Thiamine 200 mg IV Thiamine: 200 mg IV three times daily for seven days	Normal saline IV Normal saline: Normal saline IV three times daily for seven days
Measure Participants	24	28
Mean (Standard Deviation) [score on a scale]	-4.36 (14.09)	0.28 (12.17)

8. Secondary Outcome

Title	Change in Depression Scores (Month 1)
Description	Depression will be assessed using the Patient Reported Outcomes Measurement Information System - Depression (PROMIS-D) 8a short form. Scores for all PROMIS measures are reported on the T-score metric in which the mean=50 and standard deviation (SD) = 10 are centered on the general population means. Higher scores represent greater degrees of mood symptoms. Positive change scores indicate worse mood over time.
Time Frame	Baseline to one month post-transplant

Outcome Measure Data

Analysis Population Description

Participants who completed the 1 month follow-up period.

Arm/Group Title	Intervention	Control
Arm/Group Description	Thiamine 200 mg IV Thiamine: 200 mg IV three times daily for seven days	Normal saline IV Normal saline: Normal saline IV three times daily for seven days
Measure Participants	27	33
Mean (Standard Deviation) [T-score]	-1.34 (8.28)	1.16 (6.12)

9. Secondary Outcome

Title	Change in Depression Scores (Month 3)
Description	Depression will be assessed using the Patient Reported Outcomes Measurement Information System - Depression (PROMIS-D) 8a short form. Scores for all PROMIS measures are reported on the T-score metric in which the mean=50 and standard deviation (SD) = 10 are centered on the general population means. Higher scores represent greater degrees of mood symptoms. Positive change scores indicate worse mood over time.
Time Frame	Baseline to three months post-transplant

Outcome Measure Data

Analysis Population Description

Participants who completed the 3 month follow-up period

Arm/Group Title	Intervention	Control
Arm/Group Description	Thiamine 200 mg IV Thiamine: 200 mg IV three times daily for seven days	Normal saline IV Normal saline: Normal saline IV three times daily for seven days
Measure Participants	26	30
Mean (Standard Deviation) [T-score]	0.93 (6.24)	0.32 (9.53)

10. Secondary Outcome

Title	Change in Depression Scores (Month 6)
Description	Depression will be assessed using the Patient Reported Outcomes Measurement Information System - Depression (PROMIS-D) 8a short form. Scores for all PROMIS measures are reported on the T-score metric in which the mean=50 and standard deviation (SD) = 10 are centered on the general population means. Higher scores represent greater degrees of mood symptoms. Positive change scores indicate worse mood over time.
Time Frame	Baseline to six months post-transplant

Outcome Measure Data

Analysis Population Description

Participants who completed the 6 month follow-up period

Arm/Group Title	Intervention	Control
Arm/Group Description	Thiamine 200 mg IV Thiamine: 200 mg IV three times daily for seven days	Normal saline IV Normal saline: Normal saline IV three times daily for seven days
Measure Participants	24	28
Mean (Standard Deviation) [T-score]	0.14 (6.88)	-1.66 (7.89)

11. Secondary Outcome

Title	Change in Post-traumatic Stress Symptom Scores (Month 1)
Description	Post-traumatic stress symptoms will be measured using the Post Traumatic Stress Syndrome Scale 14 (PTSS-14). The PTSS-14 is a 14-item self-administered assessment. Questions are on a 7-point Likert-type Scale (1, never to 7, always) resulting in a total score between 14 and 98. Higher scores represent a more likely diagnosis of post-traumatic stress disorder (PTSD). Positive change scores indicate worse post-traumatic stress over time.
Time Frame	Baseline to one month post-transplant

Outcome Measure Data

Analysis Population Description

Participants who completed the 1 month follow-up period.

Arm/Group Title	Intervention	Control
Arm/Group Description	Thiamine 200 mg IV Thiamine: 200 mg IV three times daily for seven days	Normal saline IV Normal saline: Normal saline IV three times daily for seven days
Measure Participants	27	33
Mean (Standard Deviation) [score on a scale]	-0.52 (10.88)	1.55 (6.92)

12. Secondary Outcome

Title	Change in Post-traumatic Stress Symptom Scores (Month 3)
Description	Post-traumatic stress symptoms will be measured using the Post Traumatic Stress Syndrome Scale 14 (PTSS-14). The PTSS-14 is a 14-item self-administered assessment. Questions are on a 7-point Likert-type Scale (1, never to 7, always) resulting in a total score between 14 and 98. Higher scores represent a more likely diagnosis of post-traumatic stress disorder (PTSD). Positive change scores indicate worse post-traumatic stress over time.
Time Frame	Baseline to three months post-transplant

Outcome Measure Data

Analysis Population Description

Participants who completed the 3 month follow-up period

Arm/Group Title	Intervention	Control
Arm/Group Description	Thiamine 200 mg IV Thiamine: 200 mg IV three times daily for seven days	Normal saline IV Normal saline: Normal saline IV three times daily for seven days
Measure Participants	26	30
Mean (Standard Deviation) [score on a scale]	-1.50 (6.58)	0.83 (5.63)

13. Secondary Outcome

Title	Change in Post-traumatic Stress Symptom Scores (Month 6)
Description	Post-traumatic stress symptoms will be measured using the Post Traumatic Stress Syndrome Scale 14 (PTSS-14). The PTSS-14 is a 14-item self-administered assessment. Questions are on a 7-point Likert-type Scale (1, never to 7, always) resulting in a total score between 14 and 98. Higher scores represent a more likely diagnosis of post-traumatic stress disorder (PTSD). Positive change scores indicate worse post-traumatic stress over time.
Time Frame	Baseline to six months post-transplant

Outcome Measure Data

Analysis Population Description

Participants who completed the 6 month follow-up period.

Arm/Group Title	Intervention	Control
Arm/Group Description	Thiamine 200 mg IV Thiamine: 200 mg IV three times daily for seven days	Normal saline IV Normal saline: Normal saline IV three times daily for seven days
Measure Participants	24	28
Mean (Standard Deviation) [score on a scale]	1.79 (9.14)	1.32 (7.00)

14. Secondary Outcome

Title	Change in Cognitive Function Scores (Month 1)
Description	Cognitive function will be assessed using the Montreal Cognitive Assessment (MOCA). The MOCA is a clinician-administered tool with scores ranging from 0 to 30. Lower scores indicate worse cognitive function. Scores ≤ 25 are considered clinically significant. Positive change scores indicate better function with time.
Time Frame	From baseline to one month post-transplant

Outcome Measure Data

Analysis Population Description

One participant in the control arm was unable to complete the MoCA due to restrictions on in-person human subjects research during the COVID-19 pandemic. Otherwise, all participants available at the 1-month follow-up time point were included.

Arm/Group Title	Intervention	Control
Arm/Group Description	Thiamine 200 mg IV Thiamine: 200 mg IV three times daily for seven days	Normal saline IV Normal saline: Normal saline IV three times daily for seven days
Measure Participants	27	32
Mean (Standard Deviation) [score on a scale]	-0.70 (3.35)	-0.09 (2.76)

15. Secondary Outcome

Title	Change in Cognitive Function Scores (Month 3)
Description	Cognitive function will be assessed using the Montreal Cognitive Assessment (MOCA). The MOCA is a clinician-administered tool with scores ranging from 0 to 30. Lower scores indicate worse cognitive function. Scores ≤ 25 are considered clinically significant. Positive change scores indicate better function with time.
Time Frame	Baseline to three months post-transplant

Outcome Measure Data

Analysis Population Description

Participants who completed the 3 month follow-up period and we able to participate in the cognitive assessment. Of the 26 participants active in the thiamine arm at the 3 month follow-up, 1 did not complete this measure due to barriers related to the COVID-19 pandemic.

Arm/Group Title	Intervention	Control
Arm/Group Description	Thiamine 200 mg IV Thiamine: 200 mg IV three times daily for seven days	Normal saline IV Normal saline: Normal saline IV three times daily for seven days
Measure Participants	25	30
Mean (Standard Deviation) [score on a scale]	-0.12 (0.97)	0.97 (2.82)

16. Secondary Outcome

Title	Change in Cognitive Function Scores (Month 6)
Description	Cognitive function will be assessed using the Montreal Cognitive Assessment (MOCA). The MOCA is a clinician-administered tool with scores ranging from 0 to 30. Lower scores indicate worse cognitive function. Scores ≤ 25 are considered clinically significant. Positive change scores indicate better function with time.
Time Frame	From baseline to six months post-transplant

Outcome Measure Data

Analysis Population Description

Participants who completed the 6 month follow-up period.

Arm/Group Title	Intervention	Control
Arm/Group Description	Thiamine 200 mg IV Thiamine: 200 mg IV three times daily for seven days	Normal saline IV Normal saline: Normal saline IV three times daily for seven days
Measure Participants	24	28
Mean (Standard Deviation) [score on a scale]	0.71 (3.32)	1.54 (2.87)

17. Secondary Outcome

Title	Change in Functional Status Scores (Month 1)
Description	Functional status will be measured using the Eastern Cooperative Oncology Group (ECOG) performance scale. ECOG performance status is a single question scored on a 6-point scale (range 0 to 5) with higher scores representing greater physical restriction due to illness. Negative change scores indicate better function with time.
Time Frame	Baseline to one month post-transplant

Outcome Measure Data

Analysis Population Description

Participants who completed the 1 month follow-up period

Arm/Group Title	Intervention	Control
Arm/Group Description	Thiamine 200 mg IV Thiamine: 200 mg IV three times daily for seven days	Normal saline IV Normal saline: Normal saline IV three times daily for seven days
Measure Participants	27	33
Mean (Standard Deviation) [score on a scale]	0.70 (0.67)	0.88 (0.93)

18. Secondary Outcome

Title	Change in Functional Status Scores (Month 3)
Description	Functional status will be measured using the Eastern Cooperative Oncology Group (ECOG) performance scale. ECOG performance status is a single question scored on a 6-point scale (range 0 to 5) with higher scores representing greater physical restriction due to illness. Negative change scores indicate better function with time.
Time Frame	From baseline to three months post-transplant

Outcome Measure Data

Analysis Population Description

Participants who completed the 3 month follow-up.

Arm/Group Title	Intervention	Control
Arm/Group Description	Thiamine 200 mg IV Thiamine: 200 mg IV three times daily for seven days	Normal saline IV Normal saline: Normal saline IV three times daily for seven days
Measure Participants	26	30
Mean (Standard Deviation) [score on a scale]	0.69 (0.62)	0.60 (0.89)

19. Secondary Outcome

Title	Change in Functional Status Scores (Month 6)
Description	Functional status will be measured using the Eastern Cooperative Oncology Group (ECOG) performance scale. ECOG performance status is a single question scored on a 6-point scale (range 0 to 5) with higher scores representing greater physical restriction due to illness. Negative change scores indicate better function with time.
Time Frame	Baseline to six months post-transplant

Outcome Measure Data

Analysis Population Description

Participants who completed the 6 month follow-up period.

Arm/Group Title	Intervention	Control
Arm/Group Description	Thiamine 200 mg IV Thiamine: 200 mg IV three times daily for seven days	Normal saline IV Normal saline: Normal saline IV three times daily for seven days
Measure Participants	24	28
Mean (Standard Deviation) [score on a scale]	0.46 (0.93)	0.21 (0.63)

Adverse Events

Time Frame	Adverse event (AE) data were only collected from October 2017 through February 2020, during the intervention phase of the study and coinciding with participants' hospitalization for hematopoietic stem cell transplantation. This phase lasted up to 30 days for each participant. The study was completed on August 10, 2020, as secondary outcomes were collected for an additional 5 months after completion of AE data collection.
Adverse Event Reporting Description	Adverse events were were graded per NCI CTCAE v. 4 criteria.
Arm/Group Title	Intervention		Control
Arm/Group Description	Thiamine 200 mg IV Thiamine: 200 mg IV three times daily for seven days		Normal saline IV Normal saline: Normal saline IV three times daily for seven days
All Cause Mortality
	Intervention		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/30 (3.3%)		0/34 (0%)
Serious Adverse Events
	Intervention		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/34 (0%)
Other (Not Including Serious) Adverse Events
	Intervention		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/34 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.