Obesity's Impact on Heart Health

Overseen By Andrew McHill

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Oregon Health and Science University

Must not be taking: Prescription medications, Drugs of abuse

Disqualifiers: Smoking, Insomnia, Sleep apnea, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 5

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how obesity affects heart health, focusing on the influence of circadian rhythms on heart risks. Researchers will use special imaging techniques to observe changes in heart function in overweight individuals, particularly during stress. Participants will be divided into two groups based on body weight and will undergo a 5-day study with imaging tests. Individuals with a BMI between 18.5 and 40, who are inactive, and do not smoke or take prescription medications, may qualify for this trial. As an Early Phase 1 trial, this research aims to understand how the treatment works in people, offering participants a chance to contribute to groundbreaking insights into heart health.

Will I have to stop taking my current medications?

Yes, you will need to stop taking prescription medications to participate in this trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the treatments in this study, including 11C-CGP12177, 11C-meta-hydroxyephedrine (mHED), and O15-water, have been used in previous studies with some evidence of safety. These substances, known as radiopharmaceuticals, serve as radioactive tracers in imaging tests.

11C-meta-hydroxyephedrine (mHED) has been studied for its absorption by tissues, aiding in understanding how the body processes it. Similarly, 11C-CGP12177 is used in imaging to assess heart function. O15-water is frequently used in PET scans and is generally considered safe due to its rapid processing by the body.

Since this study is in an early phase, limited safety data is available for humans. However, the use of these radiopharmaceuticals in imaging studies suggests they are generally well-tolerated. Participants in previous studies have not reported major safety issues. As these treatments are primarily for imaging rather than direct treatment, they are expected to carry a lower risk of side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it uses advanced PET imaging techniques with unique radiopharmaceuticals like 11C-meta-hydroxyephedrine and 11C-CGP12177 to explore how obesity impacts heart health. Unlike traditional methods that might rely on more invasive procedures or less specific imaging, this trial aims to provide detailed insights into cardiovascular function and metabolism in both overweight and normal-weight individuals. By investigating these precise physiological changes, the study hopes to uncover new, targeted strategies for improving heart health in people with obesity.

What evidence suggests that this trial's treatments could be effective for obesity's impact on heart health?

Research has shown that a substance called 11C-meta-hydroxyephedrine (mHED) is useful for studying how the nervous system affects fat tissue. This is important because active brown fat can help control obesity. Another study demonstrated that 11C-CGP12177 can measure heart receptor density, which can predict improvements in heart health. In this trial, participants in both the "Overweight" and "Normal Weight" arms will undergo a 5-day circadian study protocol using these imaging techniques, along with O15-water, to explore how circadian rhythms impact heart health. Early findings suggest these imaging techniques could reveal important connections between obesity and heart health risks. ^{1 2 3 6 7}

Who Is on the Research Team?

Jeanne M Link, PhD

Principal Investigator

OHSU Center for Radiochemistry Research

Steven A Shea, PhD

Principal Investigator

Oregon Institute of Occupational Health Sciences

Are You a Good Fit for This Trial?

This trial is for adults aged 25-65 who are not very active and have a body mass index (BMI) between 18.5 to 40, meaning they range from normal weight to obese. It's not open to smokers, those with sleep issues like insomnia or severe sleep apnea, anyone on prescription meds or using drugs of abuse, or people with certain medical conditions including diabetes and high blood pressure.

Inclusion Criteria

I am between 25 and 65 years old.

Habitually sedentary

My BMI is between 18.5 and 40.

Exclusion Criteria

History of smoking/tobacco use

I have trouble sleeping.

Drugs of abuse

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Circadian Study Protocol

Participants undergo a 5-day circadian study protocol with PET imaging using radiopharmaceuticals

5 days

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the study protocol

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 11C-CGP12177
• 11C-Meta-Hydroxyephedrine (mHED)
• Circadian Study Protocol
• O15-water

Trial Overview The study is looking at how the body's daily rhythms affect heart health in overweight individuals by measuring cardiovascular risk markers at rest and in response to stress. Participants will undergo PET imaging using specific tracers like 11C-CGP12177 and mHED as well as O15-water to assess heart function.

How Is the Trial Designed?

Group I: Overweight Experimental Treatment 5 Interventions

Healthy obese \[30≤BMI\<40 and waist circumference (WC) ≥94/80 (men and women respectively)\] will participate in a 5-day circadian study protocol with PET imaging using radiopharmaceuticals (11C-meta-hydroxyephedrine, 11C-CGP12177, and O15-water).

Group II: Normal Weight Experimental Treatment 5 Interventions

Healthy lean controls \[18.5\<BMI\<25 kg/m2 and WC \<94/80 (men and women respectively)\] will participate in a 5-day circadian study protocol with PET imaging using radiopharmaceuticals (11C-meta-hydroxyephedrine, 11C-CGP12177, and O15-water).

Who Is Running the Clinical Trial?

Oregon Health and Science University

Lead Sponsor

Trials

1,024

Recruited

7,420,000+

Citations

1. clinicaltrials.eu clinicaltrials.eu/inn/o15-water/

O15-Water – Application in Therapy and Current Clinical ... This article discusses a clinical trial investigating the relationship between obesity, circadian rhythms, and cardiovascular health.

2. sciencedirect.com sciencedirect.com/science/article/pii/S221287781300029X

11C-meta-hydroxyephedrine PET/CT imaging allows in ... We analyzed 11C-MHED uptake in the interscapular BAT (iBAT) of lean and diet-induced obese (DIO) mice during activation or blockade of SNS-mediated ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05419726

Brown Adipose Tissue Activity in Response to Semaglutide ... BAT activity also increases insulin sensitivity and whole body energy expenditure, and thus has the potential to treat type 2 diabetes and obesity. Bilateral ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4452641/

Quantification of [11C]-meta-hydroxyephedrine uptake in ... The aims of this study were to determine the optimal tracer kinetic model for [11C]-meta-hydroxyephedrine ([11C]HED) and to evaluate the ...

5. jnm.snmjournals.org jnm.snmjournals.org/content/50/2/220

Myocardial β-Adrenergic Receptor Density Assessed by ... Myocardial β-Adrenergic Receptor Density Assessed by 11C-CGP12177 PET Predicts Improvement of Cardiac Function After Carvedilol Treatment in Patients with ...

6. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2016.00336/full

Preclinical In vivo Imaging for Fat Tissue Identification, ... 11C-meta-hydroxyephedrine PET/CT imaging allows in vivo study of adaptive thermogenesis and white-to-brown fat conversion. Mol. Metab. 2 ...

7. ahajournals.org ahajournals.org/doi/pdf/10.1161/circimaging.108.792408

The Future of Cardiovascular Imaging in the Diagnosis ... Radiographic, ultrasound, nuclear, and magnetic reso- nance methods have become indispensable in the man- agement of heart failure (HF).