AzTrials
AzTrials

Hematopoietic Stem Cell TransplantationPhase 2NCT03263442

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

A Phase 2 study testing Thiamine and Normal saline in people with Hematopoietic Stem Cell Transplantation and Delirium, run by UNC Lineberger Comprehensive Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Thiamine and Normal saline
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
66 participants
Where
1 siteUnited States
Study dates
16 Oct 2017to 10 Aug 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site
  • University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27514

Other trials in United States

About this study

Official title: Randomized Placebo Controlled Trial of High Dose Intravenous Thiamine for the Prevention of Delirium in Allogeneic Hematopoietic Stem Cell Transplantation

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.

Read the 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.

Being tested
Thiamine, Normal saline
Medical subject headings
Delirium, Thiamine Deficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ThiamineDrug

    Also called Thiamine Hydrochloride Injection

    200 mg IV three times daily for seven days

  • Normal salineDrug

    Also called Placebo

    Normal saline IV three times daily for seven days

Study groups in NCT03263442
Study groupRoleWhat they receive
InterventionExperimentalThiamine 200 mg IV
Receives: Drug: Thiamine
ControlPlacebo comparatorNormal saline IV
Receives: Drug: Normal saline

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)
  1. Delirium Severity

    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.

    Measured: 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

  2. Delirium Duration

    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.

    Measured: 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.

  3. Concentration of Thiamine Status Stratified by Delirium Status

    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.

    Measured: 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

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

    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.

    Measured: From baseline to one month post-transplant

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

    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.

    Measured: Baseline to three months post-transplant

  6. Change in Health-related Quality of Life Scores (Month 6)

    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.

    Measured: Baseline to six months post-transplant

  7. Change in Depression Scores (Month 1)

    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.

    Measured: Baseline to one month post-transplant

  8. Change in Depression Scores (Month 3)

    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.

    Measured: Baseline to three months post-transplant

  9. Change in Depression Scores (Month 6)

    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.

    Measured: Baseline to six months post-transplant

  10. Change in Post-traumatic Stress Symptom Scores (Month 1)

    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.

    Measured: Baseline to one month post-transplant

  11. Change in Post-traumatic Stress Symptom Scores (Month 3)

    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.

    Measured: Baseline to three months post-transplant

  12. Change in Post-traumatic Stress Symptom Scores (Month 6)

    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.

    Measured: Baseline to six months post-transplant

  13. Change in Cognitive Function Scores (Month 1)

    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.

    Measured: From baseline to one month post-transplant

  14. Change in Cognitive Function Scores (Month 3)

    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.

    Measured: Baseline to three months post-transplant

  15. Change in Cognitive Function Scores (Month 6)

    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.

    Measured: From baseline to six months post-transplant

  16. Change in Functional Status Scores (Month 1)

    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.

    Measured: Baseline to one month post-transplant

  17. Change in Functional Status Scores (Month 3)

    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.

    Measured: From baseline to three months post-transplant

  18. Change in Functional Status Scores (Month 6)

    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.

    Measured: Baseline to six months post-transplant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Aug 2017
  2. Study start16 Oct 2017
  3. Primary completion2 Mar 2020
  4. Study completion10 Aug 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
66 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03263442
Sponsor's protocol ID
LCCC1726
Other IDs
CCR-17-300
Status last verified
Sep 2021
First submitted
24 Aug 2017
Last updated
19 Oct 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 33945982

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Thiamine and Normal saline in people with Hematopoietic Stem Cell Transplantation and Delirium, run by UNC Lineberger Comprehensive Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Delirium (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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03263442, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2021.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in