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Trial record 10 of 22 for:    "Beriberi"

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

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ClinicalTrials.gov Identifier: NCT03263442
Recruitment Status : Enrolling by invitation
First Posted : August 28, 2017
Last Update Posted : October 23, 2018
Sponsor:
Collaborator:
Rising Tide Foundation
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 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 : October 16, 2017
Estimated Primary Completion Date : June 30, 2020
Estimated Study Completion Date : October 16, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Delirium

Arm Intervention/treatment
Experimental: Intervention
Thiamine 200 mg IV
Drug: Thiamine
200 mg IV three times daily for seven days
Other Name: Thiamine Hydrochloride Injection

Placebo Comparator: Control
Normal saline IV
Drug: Normal saline
Normal saline IV three times daily for seven days
Other Name: Placebo




Primary Outcome Measures :
  1. Delirium incidence [ 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. ]
    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 [ 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. ]
    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 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.

  2. Delirium duration [ 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. ]
    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. Relationship between thiamine deficiency and 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 ]
    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. Patients who develop delirium prior to the end of the thiamine treatment will not be included in this analysis. Sensitivity and specificity of this relationship will be assessed with receiver operating characteristic (ROC) curves to attempt to find a cutoff for thiamine levels that is associated with the development of delirium.

  4. Change in Health-related quality of life scores (Month 1) [ Time Frame: 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). The higher the score, the better the quality of life.

  5. Change in Health-related quality of life scores (Month 3) [ Time Frame: 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). The higher the score, the better the quality of life.

  6. Change in Health-related quality of life scores (Month 6) [ Time Frame: 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). The higher the score, the better the quality of life.

  7. Change in Depression Scores (Month 1) [ Time Frame: 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.

  8. Change in Depression Scores (Month 3) [ Time Frame: 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.

  9. Change in Depression Scores (Month 6) [ Time Frame: 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.

  10. Change in Post-traumatic stress symptom scores (Month 1) [ Time Frame: 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).

  11. Change in Post-traumatic stress symptom scores (Month 3) [ Time Frame: 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).

  12. Change in Post-traumatic stress symptom scores (Month 6) [ Time Frame: 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).

  13. Change in Cognitive function scores (Month 1) [ Time Frame: 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. It is measured on a 30-point scale with lower scores indicating greater impairment. Scores ≤ 25 are considered clinically significant.

  14. Change in Cognitive function scores (Month 3) [ Time Frame: Baseline to three months post-transplant ]
    Cognitive function will be assessed using the Montreal Cognitive Assessment (MOCA). The MOCA is a clinician administered tool. It is measured on a 30-point scale with lower scores indicating greater impairment. Scores ≤ 25 are considered clinically significant.

  15. Change in Cognitive function scores (Month 6) [ Time Frame: 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. It is measured on a 30-point scale with lower scores indicating greater impairment. Scores ≤ 25 are considered clinically significant.

  16. Change in Functional status scores (Month 1) [ Time Frame: 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 with higher scores representing greater physical restriction due to illness.

  17. Change in Functional status scores (Month 3) [ Time Frame: 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 with higher scores representing greater physical restriction due to illness.

  18. Change in Functional status scores (Month 6) [ Time Frame: 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 with higher scores representing greater physical restriction due to illness.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03263442


Locations
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United States, North Carolina
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27514
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Rising Tide Foundation
Investigators
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Study Chair: Donald Rosenstein, MD University of North Carolina, Chapel Hill
Principal Investigator: Zev Nakamura, MD University of North Carolina, Chapel Hill

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Responsible Party: University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT03263442     History of Changes
Other Study ID Numbers: 17-0298
CCR-17-300 ( Other Grant/Funding Number: Rising Tide Foundation for Clinical Cancer Research )
First Posted: August 28, 2017    Key Record Dates
Last Update Posted: October 23, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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Thiamine Deficiency
Beriberi
Delirium
Confusion
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Neurocognitive Disorders
Mental Disorders
Vitamin B Deficiency
Avitaminosis
Deficiency Diseases
Malnutrition
Nutrition Disorders
Thiamine
Vitamin B Complex
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs