What side effects are associated with this type of intervention?

Common treatments for obesity, such as phentermine and the combination of phentermine-topiramate, are associated with several side effects. These include dry mouth, constipation, and paresthesia. There is also a dose-related increase in psychiatric (e.g., depression, anxiety) and cognitive (e.g., disturbance in attention) adverse events. Additionally, while blood pressure may improve slightly, there is often an increase in heart rate. It is important to monitor these side effects and adjust treatment as necessary under medical supervision.

What prior FDA approvals exist?

Phentermine, an appetite suppressant approved by the FDA for weight management since 1959, is similar to other central nervous system stimulants used for obesity treatment. Sibutramine, another appetite suppressant, was previously approved but was removed from the market in 2010 due to increased risks of cardiovascular events. Lorcaserin, which also acted on the central nervous system to suppress appetite, was withdrawn in 2020 due to an increased occurrence of cancer in clinical trials. These examples highlight the FDA's cautious approach to approving and maintaining appetite suppressants for obesity treatment.

What other types of research exist?

Promising novel alternatives to Phentermine for obesity treatment include: 1) Metformin, which is well-tolerated and effective for weight loss, especially in patients with severe mental illness. 2) Topiramate, which may be more effective but has a higher likelihood of side effects. 3) Liraglutide, another effective option with potential side effects. 4) The fixed-dose combination of olanzapine/samidorphan, particularly for patients on or starting olanzapine to limit weight gain. These alternatives have demonstrated efficacy in clinical trials and offer different mechanisms of action and side effect profiles.

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Sympathomimetic Appetite Suppressant

Phentermine for Obesity (LEAP Trial)

Phase 4

Waitlist Available

Led By Nicholas M Pajewski, PhD

Research Sponsored by Wake Forest University Health Sciences

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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)

Be older than 18 years old

Must not have

History of glaucoma or been told by an ophthalmologist that you are at high risk for glaucoma

Diagnosis of dementia or serious mental illness (e.g., schizophrenia, bipolar disorder, severe depression)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up month 1, month 2, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24

Awards & highlights

Drug Has Already Been Approved

Pivotal Trial

Summary

This trial is studying the long-term effects of the weight-loss drug phentermine on people with obesity. The drug helps by making you feel less hungry and burning more calories. Researchers want to see if it is safe and effective over an extended period. Phentermine has been used in various formulations and combinations for weight loss, showing modest efficacy but with potential cardiovascular and psychiatric side effects.

Who is the study for?

This trial is for English-speaking adults with obesity (BMI 30-44.9 or BMI 27-29.9 with certain health issues) who are willing to follow a treatment plan and have internet access for online therapy. Women must use effective contraception. Exclusions include recent drug abuse, severe kidney/liver disease, past weight control procedures, recent use of similar medications or significant weight changes, certain heart conditions, heavy alcohol use, pregnancy/breastfeeding intentions within two years, mental health hospitalizations in the last two years.

What is being tested?

The study examines the long-term effects (up to 2 years) of phentermine on weight management and safety compared to an online lifestyle behavioral therapy program without medication. Phentermine has been FDA-approved for short-term use since 1959; this trial seeks data on its extended usage.

What are the potential side effects?

Potential side effects of phentermine may include increased blood pressure and heart rate, dry mouth, sleeplessness, nervousness and constipation. Long-term side effect profiles will be closely monitored given that phentermine is typically approved only for short-term use.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My BMI is between 30-44.9, or 27-29.9 with a weight-related health issue.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have glaucoma or am at high risk for it.

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I have been diagnosed with dementia or a serious mental illness.

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I have not used any monoamine oxidase inhibitors in the last 14 days.

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I have a history of heart or blood vessel diseases.

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I have anxiety symptoms that are not well-managed.

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I have severe kidney disease or am on dialysis.

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I have undergone a procedure to help control my weight.

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I have had an organ transplant.

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My blood pressure is high or my heart beats very fast.

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I have not had heavy alcohol use in the last 6 months.

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I have not had any cancer except for non-melanoma skin cancer in the last 5 years.

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My weight has changed by more than 5% in the last 3 months.

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I have used oral corticosteroids for more than 5 days a month in the last 3 months.

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I need extra oxygen due to severe lung problems.

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I have a history of heart valve disease.

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I have a history of irregular heartbeats.

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I am currently being treated for an overactive thyroid.

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I have a history of or currently have congestive heart failure.

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I have not had cirrhosis or symptoms of liver failure in the last 2 years.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ month 1, month 2, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~month 1, month 2, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24

This trial's timeline: 3 weeks for screening, Varies for treatment, and month 1, month 2, month 3, month 6, month 9, month 12, month 15, month 18, month 21, month 24 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Secondary study objectives

Change in Systolic Blood Pressure (mmHg)

Change in cardiac autonomic function

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

+1 more

Other study objectives

Change in body weight (%)

Change in self-reported physical activity levels

Incident cardiovascular disease or death

Awards & Highlights

Drug Has Already Been Approved

The FDA has already approved this drug, and is just seeking more data.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: PhentermineExperimental Treatment2 Interventions

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.

Group II: PlaceboPlacebo Group1 Intervention

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.

0 / 20Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for obesity often involve medications that act as appetite suppressants by stimulating the central nervous system, such as phentermine. These drugs increase the release of norepinephrine, which reduces hunger and increases energy expenditure. Other treatments include GLP-1 receptor agonists, which enhance insulin secretion and slow gastric emptying, leading to reduced appetite and food intake. These mechanisms are crucial for obesity patients as they help in reducing caloric intake and promoting weight loss, which can improve overall health and reduce the risk of obesity-related complications.