# SMART Use of Medication for the Treatment ofAdolescent Severe Obesity

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2022 · $660,609

## Abstract

Nearly 1 out of every 10 adolescents in the U.S. suffers from severe obesity (age- and sex-specific body mass
index (BMI) ≥1.2 times the 95th percentile or ≥35 kg/m2), a chronic and debilitating disease. Current treatment
guidelines call for 3 to 6 months of lifestyle modification therapy (LSMT) followed by consideration of adjunct
pharmacotherapy for patients failing to respond to LSMT alone. However, this arbitrary time recommendation
to wait 3 to 6 months before initiating medication is not evidence based. Waiting 6 months before making a
change may be too long for patients who are struggling to achieve BMI reduction. Yet, 3 months may not be
long enough to assess patient responsiveness to LSMT and could therefor lead to over medication. Further,
no guidance exists regarding how to manage patients who are non-responsive to first-line pharmacotherapy.
For adults with obesity, treatment with pharmacotherapy routinely includes combination medications, such as
phentermine+topiramate. Yet for adolescents with severe obesity, a group for whom limiting unnecessary
medication exposure is highly valued, switching from one monotherapy to another with a different mechanism
of action (e.g. switching from phentermine to topiramate) may be preferable to adding a second medication
(e.g. phentermine+topiramate). This gap in evidence-based treatment guidelines that address the optimal
timing and sequence of adjunct pharmacotherapy is difficult to fill because of the response heterogeneity to
LSMT and pharmacotherapy; using a “one-size-fits-all” approach will fail to help the non-responders and may
unnecessarily “over-treat” the responders. Instead, adaptive interventions have the potential to maximize
outcomes for more patients while limiting risk from exposure to ineffective and/or needless medications.
Specifically, adaptive interventions tailor therapy according to predictors of response and then adjust the
therapy over time based on on-going performance. Thus, the overarching goal of this clinical trial is to
garner data that will inform the development of an adaptive medical intervention for the treatment of
severe adolescent obesity that includes empirically-derived decision rules that address when adjunct
pharmacotherapy should be initiated, and if starting pharmacotherapy, what is the best sequence or
course of therapy. This study will utilize a sequential multiple assignment randomized trial (SMART)
methodology which was developed specifically for constructing adaptive interventions. One hundred fifty
adolescents (age 12-18 years) with severe obesity will be recruited in this 2-staged SMART that will
systematically examine: 1) the effect of a 3-month versus 6-month response assessment to LSMT before
starting adjunct pharmacotherapy; and 2) for non-responders to initial adjunct phentermine, the relative
effectiveness of adding topiramate to phentermine versus switching to topiramate monotherapy. All
participants will receive 12 months of intervention a...

## Key facts

- **NIH application ID:** 10435514
- **Project number:** 5R01DK119456-04
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Claudia K Fox
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $660,609
- **Award type:** 5
- **Project period:** 2019-09-15 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10435514

## Citation

> US National Institutes of Health, RePORTER application 10435514, SMART Use of Medication for the Treatment ofAdolescent Severe Obesity (5R01DK119456-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10435514. Licensed CC0.

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