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

NCT ID: NCT03263442

Last Updated: 2021-10-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-16
• Study Completion Date: 2020-08-10

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.

Conditions

Hematopoietic Stem Cell Transplantation; Delirium; Thiamine Deficiency

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Intervention

Thiamine 200 mg IV

Group Type: EXPERIMENTAL

Thiamine

Intervention Type: DRUG

200 mg IV three times daily for seven days

Control

Normal saline IV

Group Type: PLACEBO_COMPARATOR

Normal saline

Intervention Type: DRUG

Normal saline IV three times daily for seven days

Interventions

Thiamine

200 mg IV three times daily for seven days

Intervention Type: DRUG

Normal saline

Normal saline IV three times daily for seven days

Intervention Type: DRUG

Other Intervention Names

Thiamine Hydrochloride Injection; Placebo

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Rising Tide Foundation

OTHER

Sponsor Role: collaborator

UNC Lineberger Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Donald Rosenstein, MD

Role: STUDY_CHAIR

University of North Carolina, Chapel Hill

Zev Nakamura, MD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina, Chapel Hill

Locations

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 33945982 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

CCR-17-300

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

LCCC1726

Identifier Type: -

Identifier Source: org_study_id