Adolescent Obesity
Conditions
Brief summary
This study will examine the timing and sequence of using adjunct obesity pharmacotherapy for adolescents with severe obesity who do not respond to lifestyle modification therapy alone.
Detailed description
This project is studying the best time to add weight loss medication to diet and exercise for helping adolescents who carry extra weight. All participants start with a lifestyle modification program and some participants may also receive study medication.Participants must be 12-17 years of age and carry extra weight. The program will last for 48 weeks.
Interventions
BEHAVIORALLifestyle Modification Therapy (LSMT)
LSMT will consist of both in-person and by telephone sessions delivered throughout the 48-week intervention phase. Each session will last 30-60 minutes. A trained study coordinator (a registered dietician or someone trained by our registered dietician) will deliver therapy which consists of counseling using education, goal setting and barrier reduction. Participants will be randomized to receive LSMT for 12 or 24 weeks before a re-assessment of their BMI.
DRUGPhentermine Pill
Phentermine will be started only if a participant does not lose 5% of BMI after 12 or 24 weeks of LSMT. Subjects will take 15 mg of phentermine every morning for 12 weeks at which time there will be an assessment of weight loss. Subjects who achieve 5% or more BMI reduction after 12 weeks of phentermine will continue 15 mg every morning for the remainder of the study (through week 48) along with their LSMT.
DRUGTopiramate Pill
Participants who do no not achieve at least 5% BMI reduction after 12 weeks of phentermine+LSMT will be re-randomized 1:1 to either topiramate+phentermine+LSMT or topiramate+placebo+LSMT. Topiramate dosing will begin at 50 mg every morning for the first 7 days, and then increase to 100 mg every morning through week 48. At the end of week 48 the taper off will be 50 mg every morning for 7 days and then discontinue.
DRUGPlacebo
Participants who do no not achieve at least 5% BMI reduction after 12 weeks of phentermine+LSMT will be re-randomized 1:1 to either topiramate+phentermine+LSMT or topiramate+placebo+LSMT. Participants will take a placebo pill every morning.
Sponsors
University of Minnesota
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
At baseline, each participant will be randomized 1:1 to either the 12-week (Arm 1) or 24-week (Arm 2) response assessment to LSMT. This randomization will be blinded to the participant, investigator, and outcomes assessor for the duration of the study; i.e. up until 48 weeks. The second randomization includes only those participants who are non-responders to phentermine+LSMT. Each non-responder to phentermine+LSMT will be re-randomized 1:1 to either topiramate+phentermine+LSMT or topiramate+placebo+LSMT. Participants, investigators, and outcomes assessors will be blinded to phentermine/placebo. The topiramate will be open label.
Intervention model description
2-staged sequential multiple assignment randomized trial
Eligibility
Sex/Gender
ALL
Age
12 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Provision of signed and dated informed assent form; * Provision of signed and dated informed parental consent form from at least 1 legal parent/guardian; * Stated willingness to comply with all study procedures and availability for the duration of the study; * BMI \>/= 1.2 times the 95th percentile or BMI \>/= 35 Kg/m2, whichever is lower; * Tanner stage \>/= 2; * Male or female, aged 12-17 at time of consenting; * For females of reproductive potential: when sexually active, agreement to use highly effective contraception (oral contraceptive pill, intra-uterine device (IUD), or implant) during study participation; * For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner.
Exclusion criteria
* Contraindications to phentermine or topiramate use according to package inserts, including: history of glaucoma; current or recent (\< 14 days) use of monoamine oxidase inhibitor; known hypersensitivity to sympathomimetic amines; current pregnancy, plans to become pregnant, or if sexually active refusal to use 2 forms of birth control; history of cardiac disease including coronary artery disease; clinically significant cardiac arrhythmias; heart failure or uncontrolled hypertension; * Diabetes (type 1 or 2); * Presence of cardiac pacemaker; * Current or recent (\<6 months prior to enrollment) use of weight loss medication(s); * Current use of weight-altering medication(s) (e.g., atypical antipsychotic, metformin) unless dose has been stable for past 6 months; * Current use of other sympathomimetic amine such as attention-deficit hyperactivity disorder (ADHD) stimulants; * Seizure disorder (other than infantile febrile seizure); * Previous bariatric surgery; * Recent initiation of change in dose (\< 3 months prior to enrollment) of anti-hypertensive or lipid medication(s); * Tobacco use * History of or current diagnosis of schizophrenia, psychosis, mania, chemical dependency; * Unstable depression or anxiety that has required hospitalization in the past year; * Any history of suicide attempt; * Suicidal ideation or self-harm within 12 months prior to enrollment; * Bicarbonate \< 18 mmol/L; * Creatinine \> 1.2 mg/dL; * History of cholelithiasis; * History of nephrolithiasis; * Untreated thyroid disorder; * Hyperthyroidism; * Breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Body Mass Index (BMI) | Baseline to Week 48 | The outcome values represent percent change in BMI from baseline to week 48. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORClaudia Fox, MD, MPH
University of Minnesota
Participant flow
Recruitment details
Participants were recruited in the Pediatric Weight Management Clinic, by flyers and recruitment letters.
Pre-assignment details
Lifestyle Modification Therapy (LSMT): LSMT will consist of both in-person and telephone sessions delivered throughout the entirety of the 48-week intervention. Sessions will last 30-60 minutes. Phentermine Pill: Subjects will take 15 mg of phentermine every morning for 12 weeks. Topiramate Pill: Topiramate dosing will begin at 50 mg every morning for the first 7 days, and then increase to 100 mg every morning through week 48.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 19 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants |
| Race (NIH/OMB) More than one race | 15 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 101 Participants |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 24 | 0 / 20 | 0 / 21 | 0 / 16 | 0 / 19 | 0 / 20 | 0 / 19 |
| other Total, other adverse events | 11 / 11 | 20 / 24 | 20 / 20 | 21 / 21 | 16 / 16 | 19 / 19 | 20 / 20 | 19 / 19 |
| serious Total, serious adverse events | 1 / 11 | 2 / 24 | 3 / 20 | 1 / 21 | 2 / 16 | 0 / 19 | 0 / 20 | 0 / 19 |
Outcome results
None listed