# ActiveCBT for depression: Transforming treatment through exercise priming

> **NIH NIH R61** · IOWA STATE UNIVERSITY · 2024 · $715,749

## Abstract

PROJECT SUMMARY/ABSTRACT
Frontline treatments for major depressive disorder (MDD), including cognitive behavioral therapy (CBT), have
limited effectiveness, with ~½ of patients not responding to CBT and ½ relapsing within 2 years. Strategies that
could increase the potency of MDD treatments are needed. We have previously shown large psychological and
neuroplasticity improvements for 75 minutes post-exercise in adults with MDD. This creates a neurologically
fertile post-exercise window with the potential to maximize the effects of CBT performed immediately after
exercise. We have developed a novel treatment strategy using aerobic exercise to prime a subsequent CBT
session (‘ActiveCBT’). Exercise priming is hypothesized to lead to greater engagement of CBT mechanisms of
action through both common (e.g., working alliance) and specific (e.g., behavioral activation) factors linked to
depression outcomes; this CBT augmentation approach has yet to be empirically tested. Our published and
preliminary work show exercise acutely improves psychological (eg, state anhedonia) and neuroplastic (eg,
BDNF) markers in MDD, and our n=10 pilot feasibility trial of this project indicates high likelihood for logistical
success and plausible effects of exercise priming on target mechanisms. The R61 will consist of an 8-week
randomized controlled trial in 40 adults with MDD performing 30-minutes of moderate exercise or quiet rest
(ActiveCBT vs. CalmCBT) prior to weekly CBT sessions. Using a time- and attention-matched control, all
participants will view a standardized documentary series for these 30 pre-therapy minutes with the only
difference between groups being exercise. This project will also employ cutting-edge, machine learning and
natural language processing via the Lyssn platform to objectively evaluate therapy. The overall R61 goals are
to: 1) demonstrate exercise priming effects on target CBT mechanisms (working alliance and behavioral
activation), 2) link psychological and neuroplastic exercise priming to CBT mechanisms, and 3) explore
sensitivity of objective machine learning-based markers from Lyssn to ActiveCBT-induced therapy differences.
Upon identification of a moderate between-group difference in working alliance and/or behavioral activation
favoring ActiveCBT, the R33 will proceed with a 2:1 randomized, controlled trial (n=100), comparing ActiveCBT
to CalmCBT. The overall R33 goals are to: 1) confirm effects of exercise priming on target CBT mechanisms,
and 2) determine the preliminary efficacy signal of exercise priming, and determine the strength of the efficacy
link with CBT mechanisms. Our working hypotheses are that we will confirm higher working alliance and/or
behavioral activation in ActiveCBT, with greater depression effects at 8 weeks and 12 weeks later linked to
greater working alliance and/or behavioral activation. These trials will establish the potential for a subsequent
confirmatory efficacy trial to rigorously test the potential of ex...

## Key facts

- **NIH application ID:** 10846728
- **Project number:** 5R61MH129407-02
- **Recipient organization:** IOWA STATE UNIVERSITY
- **Principal Investigator:** Jacob D Meyer
- **Activity code:** R61 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $715,749
- **Award type:** 5
- **Project period:** 2023-06-01 → 2024-08-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10846728

## Citation

> US National Institutes of Health, RePORTER application 10846728, ActiveCBT for depression: Transforming treatment through exercise priming (5R61MH129407-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10846728. Licensed CC0.

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