Neurotrophic Indicators of Cognition, Executive Skills, Plasticity, and Adverse Childhood Experiences Study

NCT ID: NCT04076722

Last Updated: 2021-03-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-04
• Study Completion Date: 2020-12-11

Brief Summary

Adverse childhood experiences (ACEs) are repeatedly shown to predict negative biopsychosocial health outcomes, including obesity. High rates of ACEs in communities are often paralleled by high obesity rates, and higher ACEs, such as child abuse, have been shown to positively predict later obesity and use of unhealthy weight control behaviors. Thus, in light of the high prevalence of and potential causal links between early-life stress and obesity, there is a critical need to further explore the ACEs-obesity relationship in order to understand and to improve obesity outcomes. Given the adverse impact of ACEs and obesity on brain health, two potential high impact treatment targets of the ACEs-obesity relationship will be explored in the proposed pilot study: 1) markers of neurocognition (i.e., executive function; EF) and, 2) brain health/plasticity (i.e., neurotrophins like brain-derived neurotropic factor; BDNF and glial cell derived neurotrophic factor; GDNF).

Specifically, this trial will be the first to 1) Identify whether brain markers of neural health (e.g., neurotrophins) are related to ACES and/or neurocognitive EF performance, and 2) Test whether neuronal or glial neurotrophins predict or change in response to weight loss. Addressing these two needs advances the science of whether ACEs and EF levels are differentially related to brain indices of neural and glial health/plasticity. Results of this pilot may identify a neural substrate and/or profile by which ACEs promote obesity that may ultimately be more amenable to pharmacologic intervention in order to promote weight loss outcomes.

This group-treatment trial will assess 48 obese adults randomized to either an 8-week behavioral weight loss treatment group (n=24) or a wait list control (n=24). Our primary endpoints are percent reductions in body weight and changes in neurotrophins (e.g., BDNF, GDNF). Weight and blood specimens will be assessed at baseline, post-treatment (8-weeks), and follow-up (12-weeks). In testing these endpoints, we will meet the following aims: 1) To test whether neurotrophins are related to ACEs and executive function (EF), and 2) To test if neurotrophins predict or change in response to weight loss trajectory.

****The above description describes the study design that was terminated prematurely due to Covid-19. The following description is the modified protocol.

The treatment described above was canceled and the present study focused on the baseline visit. In this visit, participants participated in a stress reactivity protocol, so instead of looking at change in BDNF, GDNF, and inflammatory markers after weight loss treatment, we looked at change in BDNF, GDNF, and inflammatory markers after the stress activity task. This information will tell us about how ACEs status is related to these biomarkers at baseline and in response to stress.

Detailed Description

Adverse childhood experiences (ACEs) are repeatedly shown to predict negative biopsychosocial health outcomes, including obesity. High rates of ACEs in communities are often paralleled by high obesity rates, and higher ACEs, such as child abuse, have been shown to positively predict later obesity and use of unhealthy weight control behaviors. Thus, in light of the high prevalence of and potential causal links between early-life stress and obesity, there is a critical need to further explore the ACEs-obesity relationship in order to understand and to improve obesity outcomes. Given the adverse impact of ACEs and obesity on brain health, two potential high impact treatment targets of the ACEs-obesity relationship will be explored in the proposed pilot study: 1) markers of neurocognition (i.e., executive function; EF) and, 2) brain health/plasticity (i.e., neurotrophins like brain-derived neurotropic factor; BDNF and glial cell derived neurotrophic factor; GDNF).

Specifically, this trial will be the first to 1) Identify whether brain markers of neural health (e.g., neurotrophins) are related to ACES and/or neurocognitive EF performance, and 2) Test whether neuronal or glial neurotrophins predict or change in response to weight loss. Addressing these two needs advances the science of whether ACEs and EF levels are differentially related to brain indices of neural and glial health/plasticity. Results of this pilot may identify a neural substrate and/or profile by which ACEs promotes obesity that may ultimately be more amenable to pharmacologic intervention in order to promote weight loss outcomes.

This group-treatment trial will assess 48 obese adults randomized to either an 8-week behavioral weight loss treatment group (n=24) or a wait list control (n=24). Our primary endpoints are percent reductions in body weight and changes in neurotrophins (e.g., BDNF, GDNF). Weight and blood specimens will be assessed at baseline, post-treatment (8-weeks), and follow-up (12-weeks). In testing these endpoints, we will meet the following aims: Aim 1 - To test whether neurotrophins are related to ACEs and executive function (EF), and Aim 2: To test if neurotrophins predict or change in response to weight loss trajectory. To ensure the success of the trial, we have assembled a team of experts in adult behavioral obesity treatment (PI: Hawkins, PhD), neurotrophins (Consultant: Vasquez, PhD), and biostatistics (Consultant: Washburn, PhD). The results of this study will advance the science of neurocognitive risk of weight loss difficulties and their potential treatment. Our approach ensures that the neurocognitive testing and weight loss protocol can be delivered by trained non-experts, improving its scalability and future dissemination potential. The results could ultimately be used to tailor weight loss treatments such that neurocognitive risk factors related to ACES are identified early and may ultimately be proactively mitigated early in treatment to maximize participants' lasting weight loss outcomes.

****The above description describes the study design that was terminated prematurely due to Covid-19. The following description is the modified protocol.

The treatment described above was canceled and the present study focused on the baseline visit. In this visit, participants participated in a stress reactivity protocol, so instead of looking at change in BDNF, GDNF, and inflammatory markers after weight loss treatment, we looked at change in BDNF, GDNF, and inflammatory markers after the stress activity task. This information will tell us about how ACEs status is related to these biomarkers at baseline and in response to stress.

Conditions

Weight Loss; Wait-List Control

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Stress reactivity weight stigma

This study arm received a stress reactivity paradigm that involved weight stigma content in the form of an evaluated speech task.

Group Type: EXPERIMENTAL

Stress reactivity stimuli

Intervention Type: BEHAVIORAL

An evaluated speech task delivered to participants after baseline testing.

Stress reactivity non-weight stigma.

This study arm received a stress reactivity paradigm that involved non-weight stigma content in the form of an evaluated speech task.

Group Type: ACTIVE_COMPARATOR

Stress reactivity stimuli

Intervention Type: BEHAVIORAL

An evaluated speech task delivered to participants after baseline testing.

Interventions

Stress reactivity stimuli

An evaluated speech task delivered to participants after baseline testing.

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• an overweight/obese body mass index (BMI = 25 kg/m2 or greater)
• English speaking
• No use of weight loss medications in the past 3 months,
• No history of or planning to undergo bariatric surgery during the study period,
• Not currently pregnant or breastfeeding or planning to become pregnant during the study period,
• Not already enrolled in a weight loss program (e.g., Weight Watchers ®),
• No significant medical or psychiatric comorbidities, including uncontrolled metabolic disorders (e.g., thyroid, renal, liver), diabetes, heart disease, stroke, cancer, eating disorder, psychosis, mania, dementia, etc.,
• Physician determination that the study is appropriate or safe,
• Able to comply with the assessment procedures
• Able to provide informed consent or assent,
• Not planning to move during study period

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Oklahoma State University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Misty Hawkins, PhD

Role: PRINCIPAL_INVESTIGATOR

Oklahoma State University

Locations

Oklahoma State University

Stillwater, Oklahoma, United States

Countries

United States

Other Identifiers

AS1965

Identifier Type: -

Identifier Source: org_study_id