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

NCT03263442 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: LCCC1726CCR-17-300
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

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.

Conditions

Hematopoietic Stem Cell Transplantation; Delirium; Thiamine Deficiency

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Delirium

  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.

  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 (18)

• 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 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.

• 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

• Change in Health-related Quality of Life Scores (Month 1)

  From baseline to one month post-transplant

• Change in Health-related Quality of Life Scores (Month 3)

  Baseline to three months post-transplant

Study Arms (2)

Intervention

EXPERIMENTAL

Thiamine 200 mg IV

Drug: Thiamine

Control

PLACEBO COMPARATOR

Normal saline IV

Drug: Normal saline

Interventions

Thiamine DRUG

200 mg IV three times daily for seven days

Also known as: Thiamine Hydrochloride Injection

Intervention

Normal saline DRUG

Normal saline IV three times daily for seven days

Also known as: Placebo

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• Rising Tide Foundation: collaborator

Study Sites (1)

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

Related Publications (1)

• 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.

  PMID: 33945982 DERIVED

MeSH Terms

Conditions

Delirium; Thiamine Deficiency

Interventions

Thiamine; thiamine hydrochloride; Saline Solution

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Vitamin B Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Zev Nakamura
• Organization: University of North Carolina - Chapel Hill

zev_nakamura@med.unc.edu

984-974-3829

Study Officials

• Donald Rosenstein, MD

  University of North Carolina, Chapel Hill

  STUDY CHAIR

• Zev Nakamura, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2017
• First Posted: August 28, 2017
• Study Start: October 16, 2017
• Primary Completion: March 2, 2020
• Study Completion: August 10, 2020
• Last Updated: October 19, 2021
• Results First Posted: April 26, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)