Long-term Effectiveness of the Antiobesity Medication Phentermine

NCT05176626 | Active Not Recruiting Phase 4 DMC FDA Drug

• 2 other identifiers: IRB00079100UG3HL155801
• Study Type: interventional
• Target: 870
• Locations: 1 country
• Sites: 4

Brief 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 (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.

Conditions

Obesity; Drug; Obesity; Lifestyle, Healthy

Keywords

weight-loss; lifestyle intervention; phentermine

Outcome Measures

Primary Outcomes (2)

• 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.

  Baseline to month 24

• 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.

  Baseline to month 24

Secondary Outcomes (4)

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

  Baseline to month 6; Baseline to month 24

• Change in cardiac autonomic function

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

• Dependence on study drug (phentermine)

  Month 24

• Change in Systolic Blood Pressure (mmHg)

  Baseline to month 6; Baseline to month 12; Baseline to month 18

Other Outcomes (3)

• Incident cardiovascular disease or death

  Month 1, Month 2, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 21, Month 24

• Change in body weight (%)

  Baseline to month 6; Baseline to month 12

• Change in self-reported physical activity levels

  Baseline to month 6; Baseline to month 12; Baseline to month 24

Study Arms (2)

Phentermine

EXPERIMENTAL

Participants 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.

Behavioral: Online Lifestyle Behavioral Therapy; Drug: Phentermine Hydrochloride 8 MG

Placebo

PLACEBO COMPARATOR

Participants 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.

Behavioral: Online Lifestyle Behavioral Therapy

Interventions

Phentermine Hydrochloride 8 MG DRUG

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.

Also known as: Lomaira

Phentermine

Online Lifestyle Behavioral Therapy BEHAVIORAL

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; Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• Johns Hopkins University: collaborator
• Kaiser Permanente: collaborator
• HealthPartners Institute: collaborator
• The University of Texas Health Science Center, Houston: collaborator
• Biomedical Research Institute of New Mexico: collaborator
• WW International Inc: collaborator
• KVK-Tech, Inc.: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (4)

Kaiser Permanente Southern California

Los Angeles, California, 90034, United States

Location

HealthPartners Institute

Saint Louis Park, Minnesota, 55416, United States

Location

Atrium Health Wake Forest Baptist Weight Management Center

Winston-Salem, North Carolina, 27104, United States

Location

UT Center for Obesity Medicine and Metabolic Performance

Bellaire, Texas, 77401, United States

Location

Related Publications (3)

• 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.

  PMID: 41519431 BACKGROUND

• 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.

  PMID: 40836901 BACKGROUND

• 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.

  PMID: 41145317 BACKGROUND

MeSH Terms

Conditions

Obesity; Weight Loss

Interventions

Phentermine

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Body Weight Changes

Intervention Hierarchy (Ancestors)

Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals

Study Officials

• Kristina H Lewis, MD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

• Jamy D Ard, MD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

• Nicholas M Pajewski, PhD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants, study investigators and research staff, care providers, laboratory staff, and outcomes assessors will be blinded to treatment assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Blinded, placebo-matched

Study Record Dates

• First Submitted: December 15, 2021
• First Posted: January 4, 2022
• Study Start: June 30, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)