Neurotrophic Indicators of Cognition, Executive Skills, Plasticity, and Adverse Childhood Experiences Study
Condition: Weight Loss; Wait-List Control
MeSH terms: Weight Loss
Study type: Interventional

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.
    

Intervention name(s): Stress reactivity stimuli
Intervention type(s): Behavioral
Intervention description(s): An evaluated speech task delivered to participants after baseline testing.
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Obesity; Weight Loss; Adverse childhood experiences; Executive function; Brain health