Ignite Creation Date:
2024-05-06 @ 3:53 AM
Last Modification Date:
2024-10-26 @ 11:41 AM
Study NCT ID:
NCT02407704
Status:
COMPLETED
Last Update Posted:
2018-05-23
First Post:
2015-03-25
Brief Title:
A Multi-level Life-span Characterization of Adult-depression and Effects of Medication and Exercise
Sponsor:
Kirk Erickson PhD
Organization:
University of Pittsburgh
Study Overview
Official Title:
A Multi-level Life-span Characterization of Adult-depression and Effects of Medication and Exercise
Status:
COMPLETED
Status Verified Date:
2018-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MEDEX
Brief Summary:
This pilot study aims to test a model that predicts that enhanced neurotransmitter gamma-aminobutyric acid GABA function in reward and affect-regulation central nervous system CNS circuits mediates the antidepressant effects of exercise State-of-the-art magnetic resonance MR imaging cognitive assessment accelerometry genetic and inflammatory biomarkers will be acquired through the coordination of efforts from several established research programs at Western Psychiatric Institute and Clinic This pilot study will be used as a platform for testing a causalmediating role of GABA interneurons in reward processing and affect regulation in humans This pilot study is not powered for testing a full causal model but rather is intended to test overall feasibility of the intervention and acquisition of measures see specific aim 1 below This is a necessary prerequisite for designing a larger more definitive study of the model which will be a component of a future grant application Additionally the data from this study will be used to test the clinical efficacy of exercise as an adjunctive treatment for late life depression LLD Specific Aim 2 as well as imaging cognitive and sleep aims Specific Aims 3 and 4
Detailed Description:
Specific Aims
Aim 1 Establish the infrastructure protocol and procedures for recruiting screening enrolling and maintaining a sample of 30 adults both younger adults and older adults with major depression in a 12-week exercise intervention The primary aim is to establish both feasibility and proof-of-concept on a wide range of biologically and clinically relevant outcomes
Aim 2 Examine whether the 12-week physical activity pharmacotherapy intervention reduces depressive symptoms in both younger and older adults above and beyond that of treatment as usual TAU Hypothesis 1 In both younger and older adults the antidepressant properties of pharmacotherapy will be augmented when combined with aerobic exercise such that the combined intervention will have higher rates of response and remission compared to only pharmacotherapy treatment
Aim 3 Examine whether the 12-week combined physical activity and pharmacotherapy intervention changes the structural morphology in specific subfields of the hippocampus Hypothesis 1 The medication intervention will increase hippocampal volume in the dentate gyrus and carbonic anhydrase I CA1 but combining aerobic exercise with pharmacotherapy will magnify the effects of exercise Hypothesis 2 The effect on hippocampal volume will be larger for older versus younger adults Aim 4 Explore how the combination of pharmacotherapy and exercise compared with pharmacotherapy and TAU influences a range of brain and behavioral outcomes including resting state brain dynamics MR spectroscopic measures of GABA sleep efficiency and cognitive performance Hypothesis 1 Antidepressant pharmacotherapy will alter resting state networks increase GABA levels and improve sleep efficiency and cognitive performance - but these effects will be greater when combined with an aerobic exercise intervention Hypothesis 2 These effects will be moderated by age such that the effects will be greater in older adults supporting a dissociation between depression in younger and adults and providing justification for fully powered study to explore these models and treatment-predictive biomarkers
Depression is a significant global public health concern it is the second leading cause of disability worldwide and is currently estimated to affect 350 million people Antidepressant medications have shown to be more effective than placebo in treating depression However for 20-40 of individuals suffering from depression the pharmacotherapy has a slow or inadequate response Thus identifying alternative treatments for depression is a public health priority
Background
Physical activity is emerging as one of the most promising non-pharmaceutical treatments for depression Greater amounts of self-reported physical activity are associated with fewer depressive symptoms in epidemiological studies and randomized interventions find that participation in physical activity enhances mood in depressed populations A Cochrane review of 32 randomized interventions concluded that participation in physical activity is effective for reducing depressive symptoms compared to either no treatment or to a control condition Importantly antidepressants and physical activity may work through similar biological pathways to influence both mood and cognitive function In fact both antidepressants and physical activity increase levels of Brain-derived neurotrophic factor BDNF in serum and hippocampus may mitigate or reverse hippocampal atrophy influence expression and kinetics of serotonin and GABA pathways regulate brain network connectivity alter inflammatory pathways and improve sleep efficiency Our proposal aims to characterize these effects from the genetic to the behavioral and cognitive level and isolate the effects of physical activity from those of medication
Significance
If effective physical activity could become a first line of treatment for depression which might also help reduce cognitive deficits job productivity and risk of other psychiatric conditions Furthermore although physical exercise has shown promise in reducing depressive symptoms researchers still do not understand the biological pathways by which it works One of the leading hypotheses of depression is that disruptions in GABA systems underlies the deficits In contrast improvements in GABA signaling is one of the ways in which exercise may improve brain function and reduce depressive symptoms Along this line investigators hope to determine the type of exercise aerobic versus stretching and toning that can be promoted in the future to improve brain function and reduce depressive symptoms Demonstrating these links could be an important first step for developing more effective treatment plans for those suffering from depression
Aim 1 Establish the infrastructure protocol and procedures for recruiting screening enrolling and maintaining a sample of 30 adults both younger adults and older adults with major depression in a 12-week exercise intervention The primary aim is to establish both feasibility and proof-of-concept on a wide range of biologically and clinically relevant outcomes
Aim 2 Examine whether the 12-week physical activity pharmacotherapy intervention reduces depressive symptoms in both younger and older adults above and beyond that of treatment as usual TAU Hypothesis 1 In both younger and older adults the antidepressant properties of pharmacotherapy will be augmented when combined with aerobic exercise such that the combined intervention will have higher rates of response and remission compared to only pharmacotherapy treatment
Aim 3 Examine whether the 12-week combined physical activity and pharmacotherapy intervention changes the structural morphology in specific subfields of the hippocampus Hypothesis 1 The medication intervention will increase hippocampal volume in the dentate gyrus and carbonic anhydrase I CA1 but combining aerobic exercise with pharmacotherapy will magnify the effects of exercise Hypothesis 2 The effect on hippocampal volume will be larger for older versus younger adults Aim 4 Explore how the combination of pharmacotherapy and exercise compared with pharmacotherapy and TAU influences a range of brain and behavioral outcomes including resting state brain dynamics MR spectroscopic measures of GABA sleep efficiency and cognitive performance Hypothesis 1 Antidepressant pharmacotherapy will alter resting state networks increase GABA levels and improve sleep efficiency and cognitive performance - but these effects will be greater when combined with an aerobic exercise intervention Hypothesis 2 These effects will be moderated by age such that the effects will be greater in older adults supporting a dissociation between depression in younger and adults and providing justification for fully powered study to explore these models and treatment-predictive biomarkers
Depression is a significant global public health concern it is the second leading cause of disability worldwide and is currently estimated to affect 350 million people Antidepressant medications have shown to be more effective than placebo in treating depression However for 20-40 of individuals suffering from depression the pharmacotherapy has a slow or inadequate response Thus identifying alternative treatments for depression is a public health priority
Background
Physical activity is emerging as one of the most promising non-pharmaceutical treatments for depression Greater amounts of self-reported physical activity are associated with fewer depressive symptoms in epidemiological studies and randomized interventions find that participation in physical activity enhances mood in depressed populations A Cochrane review of 32 randomized interventions concluded that participation in physical activity is effective for reducing depressive symptoms compared to either no treatment or to a control condition Importantly antidepressants and physical activity may work through similar biological pathways to influence both mood and cognitive function In fact both antidepressants and physical activity increase levels of Brain-derived neurotrophic factor BDNF in serum and hippocampus may mitigate or reverse hippocampal atrophy influence expression and kinetics of serotonin and GABA pathways regulate brain network connectivity alter inflammatory pathways and improve sleep efficiency Our proposal aims to characterize these effects from the genetic to the behavioral and cognitive level and isolate the effects of physical activity from those of medication
Significance
If effective physical activity could become a first line of treatment for depression which might also help reduce cognitive deficits job productivity and risk of other psychiatric conditions Furthermore although physical exercise has shown promise in reducing depressive symptoms researchers still do not understand the biological pathways by which it works One of the leading hypotheses of depression is that disruptions in GABA systems underlies the deficits In contrast improvements in GABA signaling is one of the ways in which exercise may improve brain function and reduce depressive symptoms Along this line investigators hope to determine the type of exercise aerobic versus stretching and toning that can be promoted in the future to improve brain function and reduce depressive symptoms Demonstrating these links could be an important first step for developing more effective treatment plans for those suffering from depression
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| PRO13110090 | OTHER | None | None |
| MH090333 | OTHER_GRANT | NIH | None |