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Nicotinamide to Prevent Delirium

Primary Purpose

Delirium Confusional State

Status
Unknown status
Phase
Not Applicable
Locations
Chile
Study Type
Interventional
Intervention
Nicotinamide
Placebo tablets
Sponsored by
University of Chile
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Delirium Confusional State

Eligibility Criteria

65 Years - undefined (Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Older than 65 years old.
  • Newly admitted due to suspected coronavirus disease (COVID-19) under study.
  • To have less than 24 hours from the hospitalization at the moment of randomization.
  • Able to take medicine orally.
  • Signed an informed consent.

Exclusion Criteria:

  • An expected stay or life expectancy of less than 48 hours.
  • Severe liver dysfunction or Lewy body disease.
  • Syndromes associated with alcohol dependency and drug abuse.
  • Psychotic or bipolar disorders receiving treatment with antipsychotics.
  • Delirious at admission Patients.
  • Documented viral infections.

Sites / Locations

  • Hospital Clínico Universidad de Chile

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Nicotinamide

Control

Arm Description

Patients who meet the inclusion / exclusion criteria will be randomly assigned to the experimental group:They will continue to receive standard prevention measures: Detection of delirium, education of health care team and the patient's family, sleep hygiene plan, early mobilization, resolve sensory impairments, and delivery of information of temporal-spatial reorientation in continuously. Study medication will be managed by nurses and administered daily at 7 a.m. This regimen will be continued up to 7 days after admission. The dosage of nicotinamide will be 1,5 gr per day.

Patients who meet the inclusion / exclusion criteria will be randomly assigned to the Control group: They will continue to receive the standard prevention measures: delirium detection, treatment health team education and the patient's family, sleep hygiene plan, early mobilization, resolve sensorial deterioration, and delivery of information of temporal-spatial reorientation in a continuous manner. Study medication will be managed by nurses and administered daily at 7 a.m. (in these case placebo tablets). This regimen will be continued up to 7 days after admission.

Outcomes

Primary Outcome Measures

Incidence of delirium during the 1 week after injury.
The Confusion Assessment Method (CAM) will be used to measure delirium. CAM will be assessed between 10 and 11 a.m., and between 8 and 9 p.m. in all patients (twice a day for 7 days).

Secondary Outcome Measures

Full Information

First Posted
January 17, 2021
Last Updated
January 24, 2021
Sponsor
University of Chile
Collaborators
Fondo Nacional de Desarrollo Científico y Tecnológico, FONDECYT (Chile).
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1. Study Identification

Unique Protocol Identification Number
NCT04725253
Brief Title
Nicotinamide to Prevent Delirium
Official Title
Nicotinamide, an Inhibitor of PARP-1, for Preventing Delirium in Older Adults
Study Type
Interventional

2. Study Status

Record Verification Date
January 2021
Overall Recruitment Status
Unknown status
Study Start Date
January 21, 2021 (Anticipated)
Primary Completion Date
April 1, 2022 (Anticipated)
Study Completion Date
April 30, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Chile
Collaborators
Fondo Nacional de Desarrollo Científico y Tecnológico, FONDECYT (Chile).

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Delirium is defined as an acute change in mental status characterized by fluctuating disturbances of consciousness, attention, cognition, and perception, usually secondary to acute injuries such as trauma or infections. Delirium is more frequent in older adults, and is associated with important poor clinical outcomes including increased mortality, functional deterioration, and higher expenditures for healthcare systems. Although it is not the only one responsible, the inflammatory response plays a key role in the development of delirium. From the first descriptions of the condition 2500 years ago, it is known that patients who present with inflammatory injuries such as trauma (pe. hip fracture) or infections (sepsis), frequently develop delirium. Microglia, are an inflammatory cell with phagocytic capacity, that inhabit the nervous system and have a critical role in the regulation of the inflammatory response in the brain. It is known that microglia have receptors that respond to systemic inflammatory mediators by generating new inflammatory mediators that exert their effect on other glial cells and neurons in the central nervous system, affecting their function. Mouse models have shown that depleting the brain of microglia prevents cognitive decline after a traumatic bone injury, suggesting a role of these cells in the development of delirium. Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme that participates in DNA repair, and in the regulation of the expression of inflammatory mediators by immune cell. In vitro experiments have shown that PARP-1 enhances the microglial response to inflammation, and data from mice exposed to the bacterial component "lipo-poly-saccharide (LPS)", a classical model of delirium, showed that pharmacological inhibition of PARP-1 prevents cognitive decline secondary to that injury. Interestingly, nicotinamide, a vitamin widely available in the market, with a well-known safety profile in humans, is a well-recognized inhibitor of PARP-1. The role of PARP-1 nor nicotinamide in delirium has never been explored. Considering that, 1) there is evidence showing that PARP-1 may act as an enhancer of the inflammatory response of microglia and 2) the protective effect against cognitive impairment produced by pharmacological inhibition of PARP-1 in a mice model of delirium, we propose as hypothesis that PARP-1 participates in delirium pathogenesis by enhancing microglial activation in response to systemic inflammation. To address this hypothesis in patients, we propose to determine in a randomized clinical trial whether nicotinamide, a pharmacological inhibitor of PARP-1, is more effective than placebo for the prevention of delirium in older adults with requirement of oxygen (non-invasive) and suspected coronavirus disease (COVID-19) under study. The results of this research will contribute significantly in the field of delirium, improving the knowledge of its physiopathology, as well with the development of of new alternatives for its prevention in clinical practice.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Delirium Confusional State

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
This randomized placebo-controlled trial.
Masking
ParticipantCare Provider
Masking Description
The physician in charge will kept the randomization code, and no rater became aware of treatment allocations until requesting unmasking. Nurses were blinded except those who managed the study medication. All clinical staff, including nurses, physiotherapists or occupational therapist, will blinded. Patient and Family will be blind as well.
Allocation
Randomized
Enrollment
146 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Nicotinamide
Arm Type
Experimental
Arm Description
Patients who meet the inclusion / exclusion criteria will be randomly assigned to the experimental group:They will continue to receive standard prevention measures: Detection of delirium, education of health care team and the patient's family, sleep hygiene plan, early mobilization, resolve sensory impairments, and delivery of information of temporal-spatial reorientation in continuously. Study medication will be managed by nurses and administered daily at 7 a.m. This regimen will be continued up to 7 days after admission. The dosage of nicotinamide will be 1,5 gr per day.
Arm Title
Control
Arm Type
Placebo Comparator
Arm Description
Patients who meet the inclusion / exclusion criteria will be randomly assigned to the Control group: They will continue to receive the standard prevention measures: delirium detection, treatment health team education and the patient's family, sleep hygiene plan, early mobilization, resolve sensorial deterioration, and delivery of information of temporal-spatial reorientation in a continuous manner. Study medication will be managed by nurses and administered daily at 7 a.m. (in these case placebo tablets). This regimen will be continued up to 7 days after admission.
Intervention Type
Dietary Supplement
Intervention Name(s)
Nicotinamide
Intervention Description
Nicotinamide, 1,5 gr per day for 7 days.
Intervention Type
Other
Intervention Name(s)
Placebo tablets
Intervention Description
Placebo tablets, 1 per day for 7 days.
Primary Outcome Measure Information:
Title
Incidence of delirium during the 1 week after injury.
Description
The Confusion Assessment Method (CAM) will be used to measure delirium. CAM will be assessed between 10 and 11 a.m., and between 8 and 9 p.m. in all patients (twice a day for 7 days).
Time Frame
7 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Older than 65 years old. Newly admitted due to suspected coronavirus disease (COVID-19) under study. To have less than 24 hours from the hospitalization at the moment of randomization. Able to take medicine orally. Signed an informed consent. Exclusion Criteria: An expected stay or life expectancy of less than 48 hours. Severe liver dysfunction or Lewy body disease. Syndromes associated with alcohol dependency and drug abuse. Psychotic or bipolar disorders receiving treatment with antipsychotics. Delirious at admission Patients. Documented viral infections.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Felipe Salech, MD PhD
Phone
+56998739448
Email
fhsalech@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Daniela Ponce, Eng
Phone
+56229789405
Email
dponcedelavega@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Felipe Salech, MD PhD
Organizational Affiliation
University of Chile
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital Clínico Universidad de Chile
City
Santiago
Country
Chile
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Felipe Salech, MD PhD

12. IPD Sharing Statement

Plan to Share IPD
No

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Nicotinamide to Prevent Delirium

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