Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT03256500 |
| Other study ID # |
IRB201400807 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
September 2016 |
| Est. completion date |
June 30, 2020 |
Study information
| Verified date |
August 2018 |
| Source |
North Florida/South Georgia Veterans Health System |
| Contact |
Uma Suryadevara, MD |
| Phone |
352-548-6000 |
| Email |
uma.suryadevara[@]va.gov |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Delirium is induced by changes in cortical excitability and transcranial direct current
stimulation (tDCS), by using weak electrical fields, can modulate cortical excitability and
spontaneous firing activities in the stimulated region by shifting the resting membrane. One
half of the subjects will receive stimulation via tDCS and the other half will receive sham
tDCS for 20 minutes per day, 5 days per week, for 1 week. Symptoms will be monitored using
the Confusion Assessment Method.
Description:
Hospitalized patients with delirium, who are over age 21, will be the subjects for this
research study. This will include both men and women at the Malcom Randall Veterans Affairs
Hospital. The presence of delirium will be determined by the "Confusion Assessment Method
(CAM)" which is a standardized evidence-based tool that enables clinicians to identify
patients who are suffering with delirium. The CAM and the CAM-ICU have been reported to have
a sensitivity of 94-100% with a specificity of 89-95%, together with a high inter-rater
reliability (Wei, Fearing, Eliezer, Sternberg, & Inouye, 2008).
Patients with agitation at the moment of the procedure, pregnancy or patients with history of
epilepsy or show evidence of epilepsy on their EEG will be excluded.
As part of their routine medical care all participants will be fully evaluated for the
possible causes of delirium including: neurological disorders (CT or MRI, EEG, possible LP);
failure of vital organs (cardiac, hepatic, renal, pulmonary), metabolic disorders (e.g.
abnormalities of blood chemistries), endocrine disorders (e.g., abnormal thyroid function
tests), infections (e.g., urinary, pulmonary, sepsis), toxins-drugs-medications, and
deficiency states (B1, B12, etc). These conditions will be treated accordingly by their
primary provider. There will be no change in the rest of the care that the patient will get
when they get hospitalized.
Because patients with delirium lack the capacity to consent, the consent will be obtained
from a legally authorized representative who is usually the spouse, adult child, a relative
or a close friend. The legally authorized representative or guardian advocate who can make
decisions on the patient's behalf, will be appointed by the legal authorities. They can be a
health care surrogate/agent appointed by the person in a Durable Power of Attorney for Health
Care (DPAHC) or similar document. The legally authorized representative can also be a court
appointed guardian. If the patient/patient's legal representative decides to participate in
the study, the Principal Investigator will collect private information about the patient's
health, which is called Protected Health Information (PHI). The protected health information
will be then be coded and each subject will be given a unique identification number before
entering it into the password protected folder on the server. Once eligibility is determined,
the information is obtained from the medical records regarding psychiatric disorders,
neurological conditions, cardiac conditions, current medications, study results, age < 89 in
numerical values, sex, education level and details regarding any tests or procedures done.
A neurocognitive assessment will be done on all the patients identified as potential subjects
for the study. The assessment will be done by Uma Suryadevara, Colleen Campbell, Ronald
Shorr, Kenneth Heilman, Laurence Solberg, Andrew Pierce or Joseph Thornton. After the
assessment is done, subjects are assigned into two groups, one group that gets the sham and
group that gets the real treatment. One half of the subjects will receive sham and the other
half will receive tDCS. The Soterix Medical 1x1 line of low-intensity tDCS stimulators which
we plan to use is designed to generate low levels of direct current between one anode and one
cathode placed on the body. The current enters the body through the positive electrode, the
anode exits the body through the negative electrode, the cathode. The accessories provided
with the device allow for simple and comfortable positioning of the electrodes on the body.
The procedure will be done by Uma Suryadevara who went through the training and is certified
and Colleen Campbell will activate the sham in some patients. Laurence Solberg, Ronald shorr,
Andrew Pierce and Joseph Thornton will do the procedure after being trained. Adam Woods is
the expert in tDCS and has been teaching this procedure for sometime now and will help us
with the process. The transcranial Direct Current Stimulator has the option of activating or
deactivating the 'sham'. All participants will be treated with sham or real tDCS for 20
minutes per day, 5 days per week, for 1 week during their hospitalization. The person
performing the neurocognitive assessment will be unaware if the participant is receiving sham
or tDCS. The electrodes will be placed over the left and right frontal lobes, near the
dorsolateral prefrontal cortex, (anode on the left and cathode on the right) using the
International 10-20 system as a guide for electrode placement. (Poreisz et al., 2007; Nitsche
et al, 2012. tDCS utilizes either two saline-soaked sponge or electrode gel coated electrodes
affixed to the scalp, which causes a weak electrical current. The maximum output of the
current is 2 milliamp and each electrode has an area of 25-35 cm^2. For stimulation in the
experimental condition, a current of 1.0-2.0 milliamps will be used, which is gradually
increased and decreased to achieve this target current over 30 seconds. Vitals will be taken
before and after tDCS treatments. Both before stimulation and after stimulation on each day,
as well as daily one week after stimulation, subjects will undergo an assessment for change
in symptoms using the Memorial Delirium Assessment Scale (MDAS). Since the effects of the
stimulation may last for a short time post stimulation testing will begin approximately 5
minutes after the stimulation and be completed within one hour. Testing will also be done one
more time later that afternoon to measure the change in symptoms.
The coded information and the details of the treatment will be stored on a computer server
with secure passwords. This information will then be used to test the effects of transcranial
Direct Current Stimulation on the symptomatic treatment of delirium. The neurocognitive tests
which include both the Confusion Assessment Method and the Memorial Delirium Assessment Scale
will be used to assess the symptomatic improvement. Once this information is collected, it
will be a part of the research record for the study. This information will be retained
according to the VA policies. The subjects will get the rest of the treatment as usual. For
example, any infections will be treated, electrolyte abnormalities will be corrected,
offending agents like drugs or toxins will be discontinued, deficiencies will be corrected.
If there is any failure of vital organs or if there are any neurological disorders,
appropriate treatments will be provided as per standards. The patients will then be
discharged as appropriate.
Procedures for recruiting and consenting:
Target population: Hospitalized patients with an established diagnosis of delirium using the
'Confusion Assessment Method'.
Delirium is commonly associated with increased mortality and morbidity. It is also associated
with prolonged hospitalization, increased nursing demands and need for use of physical and
pharmacological restraints. Patients with delirium represent a vulnerable population for who
we don't have many successful treatment options. Hence, any successful symptomatic treatment
that would decrease the severity will be valuable.
Patients who are admitted to the inpatient unit, with a diagnosis of delirium based on the
'Confusion Assessment Method', are identified by the treating physician. Once the guardian
advocate or legally authorized representative is appointed by the legal authorities, consent
will be obtained for their participation in research by the physician. The guardian advocate
or legally authorized representative is usually the spouse, adult child, a relative or a
close friend. They will be given all information about the study, who to call for questions,
why the study is being done, what to expect if they participate in the study and how long the
study will last. They will also be given the risks and benefits of this study, possible
adverse reactions, the information that will be collected and who will have access to it.
They will also be made aware of the option of withdrawing from the study at any point. Once
they withdraw the health information will not be collected.
If the patient/patient's legal representative decides to participate in the study, the
Principal Investigator will collect private information about the patient's health, which is
called PHI. (Protected Health Information). The protected health information will be then be
coded before entering it into the password protected folder on the server. The information
will be collected and shared with others involved in the research to determine eligibility.
The information is obtained from the medical records regarding psychiatric disorders,
neurological conditions, cardiac conditions, current medications, study results, age < 89 in
numerical values, sex, education level and details regarding any tests or procedures done.
The information will be stored on a computer server with secure passwords. This information
will then be used to test the effects of transcranial Direct Current Stimulation on the
symptomatic treatment of delirium. The neurocognitive tests which include both the Confusion
Assessment Method and the Memorial Delirium Assessment Scale will be used to assess the
symptomatic improvement. Once this information is collected, it will be a part of the
research record for the study. People who will have access to this information will be the
Principal Investigator and research staff associated with the project.
While obtaining the informed consent, it will be explained to the legal authorized
representative that they are not required to sign the consent and the refusal will not affect
the standard treatment in any way. During the hospitalization, the participants and the
non-participants will continue to get the standard treatment for delirium. The providers will
evaluate for the cause of the delirium by: getting blood chemistries to rule out metabolic
disorders, ruling out infections (e.g., urinary, pulmonary, sepsis),
toxins-drugs-medications, deficiency states like B1, B2 etc, failure of vital organs
(cardiac, hepatic, renal, pulmonary), neurological disorders using a CT or MRI, EEG, Lumbar
Puncture if indicated. If any treatable cause is identified, it will be managed accordingly.
Meanwhile the patient will be assessed for nutritional status, reorientation techniques will
be used, sensory deficits will be corrected if present. One of the hypothesis for the
pathophysiology of delirium is changes in cortical excitability; this research intervention
can modulate cortical excitability and spontaneous firing activities in the stimulated region
by shifting the resting membrane potential leading to symptomatic improvement in a patient
with delirium.
Because Delirium is a condition that causes fluctuation in cognition, it can also cause
fluctuating decision making capacity. The psychiatrists will evaluate for decision making
capacity on an ongoing basis during the study. If it any point, the subject regains the
capacity to consent, we will go over the consenting process again with the subject. At that
point if the subject decides to withdraw from the study, the decision will be respected and
if not, the study will continue as before.
The neurocognitive assessments will be done prior to and after the treatments if they decide
to participate.
Statistical Analysis:
The major dependent variable will be the score on the CAM and the MDAS (modeled as a
continuous variable). We will perform a mixed models analysis which will compare the
trajectory of CAM and MDAS score among Experimental Participants versus Control Participants.
Because this is a pilot/exploratory study, no sample size calculations are included in this
protocol.
