Clinical trial NCT02945371: Tailored Inhibitory Control Training to Reverse EA-linked Deficits in Mid-life
Official title: Tailored Inhibitory Control Training to Reverse EA-linked Deficits in Mid-life
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Smoking
Alcohol Drinking
Prescription Drug Abuse
Substance-Related Disorders
Oral Intake Reduced
Lead sponsor: University of Oregon
Sponsor class: OTHER
First posted: 2016-10-26
Enrollment: 103
Sex: ALL
Minimum age (years): 35
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Insufficient inhibitory control is one pathway through which early adversity is related to a range of problems including excessive alcohol use, tobacco use, and unhealthy eating. The proposed research leverages a neurally informed model of inhibitory control and how it can be improved to test the efficacy of a person-centered inhibitory control intervention in a sample of mid-life individuals with early adversity. The knowledge obtained by this study could be scaled into a flexible, low-cost, and wide-ranging intervention to remediate some of the effects of early adversity on inhibitory control and thus a number of prevalent health risking behaviors.

Detailed description: Early adversity (EA) in humans is a major contributing factor to a range of deleterious physical and mental health outcomes extending through adulthood such as depression and anxiety, obesity and heart disease, and premature death. In addition to detracting significantly from individual well being and quality of life, these conditions also consume considerable resources from federal, state, and community organizations. The mechanisms through which EA exerts its effects on these outcomes are increasingly well understood, and include neurocognitive pathways related to executive function. An intervention that can successfully target, engage with, and alter the functioning of one or more of these mechanisms would be a promising way of mitigating the impact of EA on deleterious outcomes later in life. The proposed research focuses on one such pathway-deficits in inhibitory control (IC)-and tests the feasibility and efficacy of an intervention to increase functioning in that pathway in a sample of individuals who experienced EA. The intervention is grounded in a neurally informed model of change that specifies deficits in IC as an underlying causal factor common to several health-risking behaviors (HRBs). These IC deficits emerge during development as a result of a range of EA, and, critically, can be remediated in mid-life through targeted intervention. Research from our laboratory has validated an intervention that can increase IC performance and alter its underlying neural systems in young adults (Berkman, Kahn, \& Merchant, 2014). The next step in this program of research, proposed here, is to test the efficacy of that intervention in a sample of mid-life individuals who have experienced EA and the extent to which our intervention generalizes to HRBs that are prevalent in that sample. The first Aim is to test whether the intervention alters the IC system in tasks both similar to and dissimilar from the training task in terms of both behavioral performance and neural functioning. The second Aim is to test whether alterations in the functioning of the underlying neural systems mediate the effect of the intervention on performance and disinhibition-related HRBs. The two Aims will be accomplished within the context of a single randomized controlled trial (RCT) with two arms (IC training vs. active control) and pre-post measurements of IC performance, IC neural systems, and HRBs. All participants (N = 110) come to the lab for an initial assessment of behavioral / neural measures of IC and HRBs, among other measures. Then, participants are randomly assigned to receive a Person-Centered Inhibitory Control (PeCIC) training or active control training, every other day for 3-4 weeks. The PeCIC systematically pairs IC engagement with alcohol, tobacco, and/or energy-dense food cues, depending on each participant's reports of disinhibited behavior in those domains. The active control task uses personalized cues and response time tasks but does not involve IC. Finally, participants return to the laboratory for an endpoint assessment where all baseline measures are repeated. The two Aims will be robustly tested in a series of analyses comparing the behavioral and neural change from pre- to postintervention between the groups.

Eligibility criteria: Inclusion Criteria:

* Age 35-55
* Experience of early adversity (EA) before age 18 (EA is be defined as a score of 4 or higher on the Adverse Childhood Experiences (ACEs) questionnaire \[Felitti, Anda, Nordenberg, Williamson, Spitz, Edwards, et al., 1998\])
* IC difficulties such as disinhibited alcohol use, tobacco use, or food intake during adulthood. IC difficulties will be self-reported based on questions from the self-control questionnaire (Tangney, Baumeister, \& Boone, 2004) modified to be specific to alcohol, tobacco, and energy-dense food intake (e.g., "I am self-indulgent with unhealthy food at times", "I refuse alcohol when offered") using a 4-point Likert-style scale.

Exclusion Criteria:

* Individuals over age 55 will be excluded because of established functional and structural neural changes that begin to escalate at that time (Good, Johnsrude, Ashburner, Henson, Friston, \& Frackowiak, 2001; Grady, Springer, Hongwanishkul, McIntosh, \& Winocur, 2006)
* Given the high rates of morbidity for such disorders among people with high EA, we will not exclude based on past diagnoses for any of those disorders or based on current drug and alcohol use. However, we will exclude individuals who do not pass a urine toxicology screen during either of the functional magnetic resonance imaging (fMRI) sessions to ensure that the neuroimaging data are as homogeneous and reliable as possible.
* Participants who cannot undergo an MRI scan will be excluded; contraindications include metal implants (e.g., braces, pins) or metal fragments, pacemakers or other electronic medical implants, claustrophobia, pregnancy, and weight greater than 550 lbs.

Beyond these criteria, participants will be recruited without exclusions based on gender, race, or ethnicity, so our sample will reflect the diversity in the local population (Lane County, Oregon) with regard to gender, race, and ethnicity.

Primary outcomes:
measure: Inhibitory control performance, Task 1
timeFrame: 1 month
measure: Inhibitory control performance, Task 2
timeFrame: 1 month
measure: Inhibitory control neural activity
timeFrame: 1 month
Secondary outcomes:
measure: Far transfer to a task related to inhibitory control, Behavioral marker
timeFrame: 1 month
measure: Far transfer to a task related to inhibitory control, Neural marker
timeFrame: 1 month
measure: Health-risking behavior
timeFrame: 1 month, 3 months
Other outcomes:
Locations:
city: Eugene
country: United States
facility: University of Oregon, Social and Affective Neuroscience Laboratory
state: Oregon
Study officials:
affiliation: University of Oregon
name: Elliot T Berkman, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fisher PA, Berkman ET. Designing Interventions Informed by Scientific Knowledge About Effects of Early Adversity: A Translational Neuroscience Agenda for Next Generation Addictions Research. Curr Addict Rep. 2015 Dec 1;2(4):347-353. doi: 10.1007/s40429-015-0071-x. Epub 2015 Sep 28.
citation: Berkman ET, Lukinova E, Menshikov I, Myagkov M. Sociality as a natural mechanism of public goods provision. PLoS One. 2015 Mar 19;10(3):e0119685. doi: 10.1371/journal.pone.0119685. eCollection 2015.
citation: Giuliani NR, Tomiyama AJ, Mann T, Berkman ET. Prediction of daily food intake as a function of measurement modality and restriction status. Psychosom Med. 2015 Jun;77(5):583-90. doi: 10.1097/PSY.0000000000000187.