Clinical trial NCT01591759: A Pilot Trial of Citicoline in Individuals With Mild Traumatic Brain Injury (mTBI)
Official title: A Pilot Trial of Citicoline in Individuals With mTBI
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Traumatic Brain Injury
Keywords: citicoline
cognitive function
function magnetic resonance imaging
magnetic resonance spectroscopy
diffusion tensor imaging
Lead sponsor: Mclean Hospital
Sponsor class: OTHER
First posted: 2012-05-04
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This investigation will explore the impact of 8 weeks of citicoline treatment on cognitive function, clinical state and substance use in 40 individuals with mild traumatic brain injury (mTBI).

Detailed description: Traumatic brain injury (TBI) remains a major cause of death and disability within the United States. Approximately 1.4 million individuals sustain a TBI each year, and currently, more than 5.3 million Americans or 3% of the general population live with disabilities associated with a TBI, resulting in enormous financial, physical and psychosocial burdens to the patients, their families and society. The issue of TBI has never been more salient, as it is now labeled the "signature wound" of the current conflict in Iraq and Afghanistan.

Patients with mTBI often experience a variety of symptoms including headache, dizziness, fatigue, irritability, depression, anxiety, insomnia, reduced alcohol tolerance, and problems with cognitive function. In acute stages, cognitive deficits may affect multiple domains and be severe enough to interfere with everyday activities.

The proposed investigation will explore the impact of 8 weeks of citicoline treatment on cognitive function, clinical state and substance use in 40 individuals with mTBI. The investigators hypothesize that individuals with mTBI who receive citicoline will demonstrate improvements in cognitive performance relative to their own pre-treatment levels as well as to those randomized to placebo. Specifically, the investigators expect the greatest improvement on frontal/executive measures following treatment with citicoline. In addition, the investigators also hypothesize that 8 weeks of treatment with citicoline will result in a reduction of comorbid substance use and improvements in clinical state measures relative to both pre-treatment levels and those randomized to receive placebo. Given the relationship between cognitive function and clinical state, the investigators expect a primary improvement in cognitive function will likely precede the expected improvement of mTBI-related symptoms.

Eligibility criteria: Inclusion Criteria:

* Subject is able to provide informed consent
* Subject is cooperative
* Subject is between 18 and 35 years of age (inclusive)
* Subject meets criteria for mTBI
* Subject has separate treating physician and is willing to provide consent for treating physician to be contacted by research team
* Subject is a native English speaker or acquired English prior to age 5

Exclusion Criteria:

* Serious medical illness, including diabetes, neurodegenerative disorder (i.e. multiple sclerosis, lupus, etc)
* Neurological disorder or history of serious head trauma resulting in loss of extended loss of consciousness or coma
* History of ECT treatment
* Estimated IQ \< 75
* Positive urine pregnancy test (screened on all study visits)

Additional MR Imaging Exclusion Criteria:

* Presence of a medical condition known to affect MR BOLD imaging (i.e. metabolism disorders, eating disorders, hormonal dysregulation, etc)
* Uncorrectable poor vision, as subjects must have normal or corrected-to normal vision for viewing of cognitive challenge paradigms during fMRI protocols
* Claustrophobia or metal implanted within the body, including body piercings which are not removable
* Additional MR related contraindications:

  * Cardiac pacemakers
  * Metal clips on blood vessels (also called stents)
  * Artificial heart valve, artificial arms, hands, legs, etc.
  * Brain stimulator devices
  * Implanted drug pumps
  * Ear or eye implants
  * Known metal fragments in eyes
  * Exposure to metal filings (sheetmetal workers, welders, and others)
  * Other metallic surgical hardware in vital area
  * Certain tattoos with metallic ink
  * Certain transdermal (skin) patches such as:
  * NicoDerm (nicotine for tobacco dependence)
  * Transderm Scop (scopolamine for motion sickness)
  * Ortho Evra (birth control)
  * Certain intrauterine devices (IUDs containing metal)
* Since some will be military veterans with combat experience and may have been exposed to shrapnel, they will be screened with a handheld metal detector to ensure that they do not have any metal embedded in their body. Subjects who do not pass the metal detector screen and subjects with known shrapnel or other metal embedded or implanted in their body will not be eligible to participate in the MRI portion of this study.

Primary outcomes:
measure: Neurocognitive Assessment Changes with Citicoline Treatment
timeFrame: At baseline and at treatment week 4 and week 8
Secondary outcomes:
measure: Clinical State Assessment Changes with Citicoline Treatment
timeFrame: Weekly assessment & biweekly clinical scales for 8 weeks
measure: Functional MRI and Diffusion Tensor Imaging Changes with Citicoline Treatment
timeFrame: At baseline and at treatment week 8
measure: Magnetic Resonance Spectroscopy Changes with Citicoline Treatment
timeFrame: At baseline and at treatment week 8
Other outcomes:
Locations:
city: Belmont
country: United States
facility: McLean Hospital Brain Imaging Center
state: Massachusetts
Study officials:
affiliation: Mclean Hospital
name: Staci A Gruber, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Mclean Hospital
name: Scott E Lukas, Ph.D.
role: STUDY_CHAIR
References: