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ObesityPhase 4LEAPNCT05176626

Long-term Effectiveness of the Antiobesity Medication Phentermine

A Phase 4 study testing Online Lifestyle Behavioral Therapy and Phentermine Hydrochloride 8 MG in people with Obesity and Obesity; Drug, run by Wake Forest University Health Sciences at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this research study is to understand the long-term effects of the drug phentermine on weight, blood pressure, other health outcomes, and safety. Phentermine has been approved by the US Food and Drug Administration (FDA) for weight management since 1959, but it has not been approved for long-term use… Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Obesity, Obesity; Drug, Lifestyle, Healthy
What is being tested?
Online Lifestyle Behavioral Therapy and Phentermine Hydrochloride 8 MG
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
870 participants
Where
4 sitesUnited States
Study dates
30 Jun 2022to 30 Sep 2026
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • BMI 30-44.9 kg/m2 or BMI 27-29.9 with weight related comorbidity (including hypertension, prediabetes, type 2 diabetes mellitus, dyslipidemia, nonalcoholic fatty liver disease, treated obstructive sleep apnea, osteoarthritis, low back pain, gastroesophageal reflux disease)
  • English-speaking
  • Has a smartphone or other device with regular internet access
  • Interested in and willing to lose weight as a result of treatment
  • Able to take oral medication and willing to adhere to the clinical visit schedule for the trial and lifestyle based treatment regimen throughout the study duration, as recommended by the study clinician
  • For females of reproductive potential: use of effective contraception for at least 1 month prior to randomization and agreement to use such a method during study participation and for an additional 8 weeks after the end of study drug administration
  • Provision of electronically-signed consent form
  • Stated willingness to comply with all study procedures and availability for the duration of the study

Who cannot join

  • History of coronary artery, cerebrovascular or peripheral arterial disease including myocardial infarction, unstable angina, revascularization, stroke/TIA, carotid intervention, claudication
  • Poorly-controlled blood pressure (>149/94) or elevated heart rate (>110 bpm)
  • History of cardiac arrhythmia
  • Active / currently-treated hyperthyroidism
  • History of glaucoma or been told by an ophthalmologist that you are at high risk for glaucoma
  • Heavy alcohol use within the last 6 months (men: more than 4 drinks on any day or more than 14 drinks per week; women: more than 3 drinks on any day or more than 7 drinks per week)
Show all 36Show fewer
  • History of substance use disorder or active use of illicit substances within the last 12 months. Tetrahydrocannabinol (THC)-containing products will not be considered an illicit substance.
  • Use of a drug in the monoamine oxidase inhibitor class, currently or within the last 14 days
  • Currently pregnant or lactating/breastfeeding; intention to get pregnant in next 24 months; seeking or in active treatment for infertility
  • End-stage renal disease on dialysis or CKD class IV or higher (eGFR <30)
  • History of valvular heart disease
  • Congestive heart failure (any history or current)
  • Cirrhosis or symptoms of liver failure in the last 2 years
  • Severe pulmonary disease requiring supplemental oxygen
  • Quit using nicotine-containing products less than 6 months prior to baseline visit or intention to quit use in the next 2 years
  • Use of oral corticosteroids more than 5 days/month in the last 3 months
  • Elevated depressive symptoms
  • Uncontrolled anxiety symptoms
  • Hospitalization for mental illness in the last 24 months
  • Diagnosis of dementia or serious mental illness (e.g., schizophrenia, bipolar disorder, severe depression)
  • Binge Eating Disorder, Bulimia or Anorexia Nervosa diagnosis or treatment within the last 2 years
  • Prior procedure for weight control (including bariatric surgery, devices)
  • Use of phentermine, phentermine-containing medication, or anti-obesity medication with similar mechanism of action to phentermine (e.g., phendimetrazine or diethylpropion) in the previous 24 months
  • Use of any non-phentermine-containing medications prescribed for weight loss in previous 12 months
  • Unstable dose of weight-loss-promoting medications within the last 12 months. Weight-loss-promoting medications are medication prescribed for another condition, but are known to have weight loss effects. Examples would include use of a GLP1 agonist or SGLT2 inhibitor in patients with diabetes; use of topiramate among patients with migraine headaches.
  • Use of any stimulant medications in previous 12 months
  • Known allergy or intolerance to phentermine or phentermine-containing medication
  • Documented or self-reported weight change (gain or loss) of more than 5% of current body weight in the past 3 months
  • History of cancer other than non-melanoma skin cancer in the past 5 years
  • History of organ transplantation
  • Plan to move outside the area in the next two years
  • Unable to make changes to diet (e.g., severe food allergies or intolerances; medically necessary aspects of diet incompatible with intervention)
  • Already participating in another research study that includes lifestyle changes and/or study medication or has participated in such a study within the last 12 months
  • Total body weight that exceeds 400 lbs., precluding use of the digital scale in the lifestyle intervention
  • Upper arm circumference that exceeds 50 cm, precluding use of the OMRON HEM 907 XL to measure blood pressure
  • Other concern or medical comorbidity that, per discretion of study clinician, would render the participant unfit or unable to safely take part in the 24-month intervention

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • UT Center for Obesity Medicine and Metabolic Performance

    Bellaire, Texas, 77401

  • Kaiser Permanente Southern California

    Los Angeles, California, 90034

  • HealthPartners Institute

    Saint Louis Park, Minnesota, 55416

  • Atrium Health Wake Forest Baptist Weight Management Center

    Winston-Salem, North Carolina, 27104

Other trials in United States

About this study

The purpose of this research study is to understand the long-term effects of the drug phentermine on weight, blood pressure, other health outcomes, and safety. Phentermine has been approved by the US Food and Drug Administration (FDA) for weight management since 1959, but it has not been approved for long-term use (i.e., treatment lasting more than 12 weeks). This trial is designed to learn about the long-term effects of phentermine for up to 2 years because obesity is a chronic disease and expert guidelines recommend long-term use of anti-obesity medications as one treatment option.

Read the detailed description

The Long-term Effectiveness of the Anti-obesity medication Phentermine (LEAP) trial, a placebo-controlled, randomized trial, will be conducted at 5 clinical sites across the United States. All participants will be provided with an evidence-based online lifestyle intervention, and participants receiving 24 mg/day of phentermine vs. a placebo for up to 24 months will be compared in an intent-to-treat fashion. The co-primary outcomes of percent weight loss and change in systolic blood pressure at 24 months will be examined. Also, between group changes in drivers of energy balance, including resting metabolic rate, caloric intake, physical activity and dietary composition will be compared. To explore the effects of weight loss on cardiometabolic health, changes in heart rate, hemoglobin A1c, lipids, waist circumference, atherosclerotic cardiovascular disease (ASCVD) risk score, and novel ECG markers of cardiac strain will be compared. Overall adverse event and serious adverse event rate, including rates of incident cardiovascular disease or death, will be measured.

Being tested
Online Lifestyle Behavioral Therapy, Phentermine Hydrochloride 8 MG
Keywords
weight-loss, lifestyle intervention, phentermine
Medical subject headings
Obesity, Weight Loss

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Online Lifestyle Behavioral TherapyBehavioural

    Participants will receive access to the WW™ digital application for the duration of their participation. The WW™ digital application can be accessed using a smartphone, tablet or personal computer and includes functions such as food journaling, progress charts, lifestyle coaching , ability to manually enter exercise data or link with a fitness tracking device, incentives for behavior change, recipes, and local restaurant recommendations using GPS. Over the course of 12 clinic visits with an obesity provider, participants will be prescribed a dietary plan based on the WW™ app and will be asked to journal dietary intake.

  • Phentermine Hydrochloride 8 MGDrug

    Also called Lomaira

    At the randomization visit, participants will be started on 8 mg PO daily of phentermine or placebo, with a recommendation to take the medication in the morning. They will be provided with detailed instructions on how to increase their dose of study drug over the subsequent weeks. After one week, participants will increase to 16 mg daily. After the second week, participants will further increase their dose to 24 mg daily and at the 1-month in-person follow-up, participants who tolerate the 24 mg dose will be maintained on this as the maximum daily dose for a total of 24 months. For participants who do not tolerate an escalation in medication dose due to side effects, adverse events, and/or elevations in blood pressure and/or heart rate, the study clinician may adjust the dose and/or delay dose escalation. Study clinicians will work with participants to achieve and sustain the maximum dose tolerated.

Study groups in NCT05176626
Study groupRoleWhat they receive
PhentermineExperimentalParticipants randomized to active treatment in LEAP will be provided with phentermine hydrochloride 8 mg scored tablets. This formulation of the drug is commercially available and marketed as Lomaira TM.
Receives: Behavioral: Online Lifestyle Behavioral Therapy; Drug: Phentermine Hydrochloride 8 MG
PlaceboPlacebo comparatorParticipants randomized to the control arm of LEAP will be provided with placebo tablets consisting of cellulose and corn starch and manufactured to have the same characteristics of the active drug, including size, shape, weight, and sensory perceptions.
Receives: Behavioral: Online Lifestyle Behavioral Therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in body weight (%)

    The primary outcome for efficacy will be percent weight loss at 24 months of follow-up, relative to body weight (kg) at randomization.

    Measured: Baseline to month 24

  2. Change in Systolic Blood Pressure (mmHg)

    The primary outcome to address phentermine's impact on a key cardiovascular disease risk factor, blood pressure, will be assessed at 24 months. Staff will measure BP using a standardized protocol with automated BP measurement devices (Omron HEM907XL) and following standard clinical practice guidelines for blood pressure measurement.

    Measured: Baseline to month 24

Secondary outcomes (4)

  1. Change in resting energy expenditure (REE) / resting metabolic rate (RMR)

    RMR will be measured via indirect calorimetry using the KORR ReeVue (KORR Medical Technologies, Salt Lake City, UT).

    Measured: Baseline to month 6; Baseline to month 24

  2. Change in cardiac autonomic function

    Change in cardiac autonomic function will be measured using heart rate variability with electrocardiogram (ECG). Heart rate variability (HRV) and resting heart rate (RHR) are noninvasive measures of cardiac autonomic function.

    Measured: Baseline to month 3; Baseline to month 6; Baseline to month 12; Baseline to month 24

  3. Dependence on study drug (phentermine)

    Dependence on study drug will be assessed using the Severity of Dependence Scale (SDS), a brief 5-item validated measure of psychological dependence that has been used for both illegal drugs of abuse and prescription drugs with concern for addiction potential. The score ranges from 0-15 with a higher score denoting a stronger dependence on the study drug.

    Measured: Month 24

  4. Change in Systolic Blood Pressure (mmHg)

    To address phentermine's impact on blood pressure over the course of the study, change in systolic blood pressure will be assessed at 6 months using a standardized measurement protocol with automated BP devices and following standard clinical practice guidelines for blood pressure measurement.

    Measured: Baseline to month 6; Baseline to month 12; Baseline to month 18

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Jan 2022
  2. Study start30 Jun 2022
  3. Primary completion30 Sep 2026
  4. Study completion30 Sep 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Blinded, placebo-matched
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
870 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05176626
Sponsor's protocol ID
IRB00079100
Other IDs
UG3HL155801
Acronym
LEAP
Status last verified
Nov 2026
First submitted
15 Dec 2021
Last updated
5 Nov 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Young CB, Rives E, Gudzune KA, Jaeger BC, Simmons CG, White BN, Hooker SA, Horn DB, Young DR, Vesely J, Velazquez A, Price C, Cook SD, Martin-Fernandez K, Inzhakova G, Pajewski NM, Ard JD, Lewis KH. The long-term effectiveness of the anti-obesity medication phentermine (LEAP) trial: Rationale, design, and baseline characteristics. Contemp Clin Trials. 2026 Feb;161:108219. doi: 10.1016/j.cct.2026.108219. Epub 2026 Jan 8.

    PubMed 41519431

  • Ziegenfuss JY, Sour EU, Roelofs EJ, Vesely JM, Margolis KL, Hooker SA. A randomized study comparing patient portal and email communications for trial recruitment. Clin Trials. 2025 Oct;22(5):597-606. doi: 10.1177/17407745251358259. Epub 2025 Aug 21.

    PubMed 40836901

  • Heeren FAN, Ruddiman KR, Simmons C, White BN, Jaeger BC, Pajewski NM, Hooker SA, Horn DB, Martin-Fernandez K, Gudzune KA, Young CB, Ard J, Lewis KH. Application of the Lancet Commission Criteria for the Diagnosis of Obesity to a Clinical Trials Population: The LEAP Trial. Obesity (Silver Spring). 2026 Jan;34(1):58-64. doi: 10.1002/oby.70070. Epub 2025 Oct 27.

    PubMed 41145317

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Online Lifestyle Behavioral Therapy and Phentermine Hydrochloride 8 MG in people with Obesity and Obesity; Drug, run by Wake Forest University Health Sciences at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in body weight (%) (time frame: Baseline to month 24). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05176626, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2026.

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