Angiotensin-(1-7) for Obesity and High Blood Pressure

Overseen By Amy Arnold, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Milton S. Hershey Medical Center

Must be taking: Antihypertensives

Must not be taking: SNRIs, Stimulants, Anticoagulants, others

Disqualifiers: Diabetes, Cardiovascular disease, Drug abuse, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 2 visits, each separated by at least 1 week

52 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop all current medications, but you cannot be on more than two antihypertensive medications or certain other treatments like SNRIs, anticoagulants, or investigational drugs. Check with the trial team for details.

What data supports the idea that Angiotensin-(1-7) for Obesity and High Blood Pressure is an effective treatment?

The available research shows that Angiotensin-(1-7) can help manage obesity and high blood pressure by affecting the body's metabolism and reducing the negative effects of another substance called Angiotensin II, which is linked to these conditions. Studies suggest that Angiotensin-(1-7) can improve how the body processes fats and sugars, which are important factors in obesity and related health issues. Additionally, treatments that block the renin-angiotensin system, which includes Angiotensin-(1-7), have shown benefits in managing obesity-related high blood pressure and improving overall heart health. This suggests that Angiotensin-(1-7) could be a promising option for treating these conditions. ^{1 2 3 4 5}

What safety data exists for Angiotensin-(1-7) treatment?

The provided research does not directly address safety data for Angiotensin-(1-7) treatment. However, it highlights its potential therapeutic roles in metabolic disorders, cardiovascular protection, and its involvement in the renin-angiotensin system. Further specific studies on safety data would be needed to comprehensively answer this question. ^{1 4 6 7 8}

Is the drug Angiotensin-(1-7) a promising treatment for obesity and high blood pressure?

Yes, Angiotensin-(1-7) is a promising drug for treating obesity and high blood pressure. It helps regulate blood pressure and metabolism, counteracts negative effects of another hormone called Angiotensin II, and has shown positive results in both animal and human studies for improving metabolic health. ^{1 4 7 9 10}

What is the purpose of this trial?

Obesity is a global health concern that is associated with high blood pressure and an increased risk for developing cardiovascular disease. The purpose of this study is to find out if the investigational drug angiotensin-(1-7) can improve cardiovascular health in people with obesity and high blood pressure.

Research Team

Amy Arnold, PhD

Principal Investigator

Pennsylvania State University College of Medicine

Eligibility Criteria

This trial is for individuals who are dealing with obesity and high blood pressure, aiming to explore if angiotensin-(1-7) can enhance heart health. Specific eligibility details are not provided.

Inclusion Criteria

I understand the study and can agree to participate.

I am a person of any gender or race.

Body mass index (BMI) between 30-40 kg/m2

Exclusion Criteria

I do not have a specific condition causing high blood pressure.

I have difficulty making decisions due to a mental condition.

Highly trained athletes

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 visit

1 visit (in-person)

Treatment

Participants receive intravenous angiotensin-(1-7) or saline infusion in a crossover design

2 visits, each separated by at least 1 week

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Angiotensin-(1-7)

Trial Overview The study investigates the cardiovascular effects of angiotensin-(1-7) compared to saline (a placebo), in people with obesity-related hypertension.

Participant Groups

Group I: Angiotensin-(1-7) Experimental Treatment 1 Intervention

Participants will receive intravenous angiotensin-(1-7) at one study visit for a total of 120 minutes. Angiotensin-(1-7) will be given in escalating doses of 2 ng/kg/min, 4 ng/kg/min, and 8 ng/kg/min. Each of these doses will be infused for 10 minutes. Following this 30 minute dose escalation period, angiotensin-(1-7) will be given at 8 ng/kg/min for an additional 90 minutes. Infusion rates will be calculated for each patient based on body mass.

Group II: Saline Placebo Group 1 Intervention

Participants receive intravenous saline at one study visit for a total of 120 minutes. The volume of saline will match the volume of angiotensin-(1-7) infused. Infusion rates will be calculated for each patient based on body mass.

Angiotensin-(1-7) is already approved in United States, European Union for the following indications:

Approved in United States as TXA127 for:

• Duchenne muscular dystrophy (DMD)
• Limb-girdle muscular dystrophy (LGMD)
• Congenital muscular dystrophy MDC1A
• Marfan syndrome
• Dystrophic Epidermolysis Bullosa (DEB)
• Pulmonary arterial hypertension
• Myelodysplastic Syndrome (MDS)

Approved in European Union as TXA127 for:

• Duchenne muscular dystrophy (DMD)

Who Is Running the Clinical Trial?

Milton S. Hershey Medical Center

Lead Sponsor

Trials

515

Recruited

2,873,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Findings from Research

Angiotensin-(1-7) has shown potential as a therapeutic agent for treating and preventing metabolic disorders, particularly in the context of rising obesity and metabolic syndrome rates worldwide.

The activation of the ACE2/Ang-(1-7)/Mas pathway may counteract the negative effects of Angiotensin II, which is linked to appetite regulation and fat metabolism, suggesting a promising approach for managing metabolic diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Angiotensin 1-7: a peptide for preventing and treating metabolic syndrome. Santos, SH., Andrade, JM.[2020]

Obesity is a significant risk factor for hypertension and is often accompanied by issues like insulin resistance and dyslipidemia, which can lead to serious health complications such as left ventricular hypertrophy and increased inflammation.

Antihypertensive medications that target the renin-angiotensin system, like ACE inhibitors and angiotensin receptor blockers, may not only lower blood pressure but also improve metabolic health and protect against organ damage in obese patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there a rationale for angiotensin blockade in the management of obesity hypertension? Sharma, AM.[2016]

The renin-angiotensin system is linked to obesity and metabolic diseases, influencing appetite, metabolism, and fat tissue growth, as shown by various animal and human studies.

New pharmaceuticals that inhibit the renin-angiotensin system, originally designed for treating hypertension and heart failure, may also be effective in addressing obesity and metabolic disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of angiotensin in obesity and metabolic disease. Mathai, ML., Chen, N., Cornall, L., et al.[2019]

Angiotensin II (Ang II) plays a significant role in metabolism and may contribute to obesity-related conditions like hypertension and type 2 diabetes by acting through its receptors in adipose tissue.

The review discusses how Ang II is produced and its signaling pathways, as well as the potential of pharmaceutical agents targeting the renin-angiotensin system (RAS) to treat obesity-related disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Possible involvement of the adipose tissue renin-angiotensin system in the pathophysiology of obesity and obesity-related disorders. Goossens, GH., Blaak, EE., van Baak, MA.[2019]

In a study involving 12 non-obese and 11 obese men, the application of Angiotensin II (Ang II) resulted in subtle changes in tissue metabolism and blood flow, but did not show a significant increase in responsiveness to Ang II in obese individuals.

Obese subjects exhibited higher baseline levels of certain metabolites in adipose tissue and muscle, indicating altered metabolic responses, yet the overall effects of Ang II on tissue perfusion and metabolism were minimal across both groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemodynamic and metabolic responses to interstitial angiotensin II in normal weight and obese men. Boschmann, M., Adams, F., Schaller, K., et al.[2006]

Angiotensin-(1-7) (Ang-[1-7]) protects heart cells from high glucose-induced damage by inhibiting the reactive oxygen species-leptin-p38 MAPK/ERK1/2 pathways, which are activated during diabetic conditions.

In laboratory tests on H9c2 heart cells, Ang-(1-7) treatment led to increased cell viability, reduced apoptosis, and lower reactive oxygen species production, demonstrating its potential as a therapeutic agent in diabetic cardiovascular diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Angiotensin-(1-7) protects cardiomyocytes against high glucose-induced injuries through inhibiting reactive oxygen species-activated leptin-p38 mitogen-activated protein kinase/extracellular signal-regulated protein kinase 1/2 pathways, but not the leptin-c-Jun N-terminal kinase pathway in vitro. Lei, Y., Xu, Q., Zeng, B., et al.[2022]

In a study of 175 adolescents born prematurely, those with overweight or obesity showed significantly higher levels of angiotensin II (Ang II) and lower levels of angiotensin-(1-7), indicating an imbalance in the renin-angiotensin system that could contribute to health issues.

This imbalance was associated with higher blood pressure, suggesting that obesity may increase the risk of hypertension and cardiovascular disease in preterm-born individuals by exacerbating existing cardiovascular risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obesity is Associated with Higher Blood Pressure and Higher Levels of Angiotensin II but Lower Angiotensin-(1-7) in Adolescents Born Preterm. South, AM., Nixon, PA., Chappell, MC., et al.[2020]

Angiotensin 1-7 (ANG 1-7) has been shown to dilate human microvessels, but this effect is significantly reduced in patients with coronary artery disease (CAD).

Treatment with ANG 1-7 can restore the nitric oxide (NO) component of flow-mediated dilation in arterioles from CAD patients, and this effect is dependent on telomerase activity, highlighting its potential as a vasoprotective agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vascular Actions of Angiotensin 1-7 in the Human Microcirculation: Novel Role for Telomerase. Durand, MJ., Zinkevich, NS., Riedel, M., et al.[2021]

Mas receptor (MasR) deficiency in female mice removes their protection against obesity-induced hypertension, while in male mice, it leads to lower blood pressure despite obesity-related cardiac dysfunction.

Infusion of angiotensin-(1-7) (ANG-(1-7)) can restore cardiac function in male mice with MasR, but not in those lacking the receptor, suggesting that MasR agonists could be potential therapies for cardiovascular issues related to obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential effects of Mas receptor deficiency on cardiac function and blood pressure in obese male and female mice. Wang, Y., Shoemaker, R., Powell, D., et al.[2021]

Chronic infusion of angiotensin-(1-7) in obese female mice improved glucose tolerance, highlighting a significant sex difference in response to this treatment compared to male mice, who showed similar insulin sensitivity but did not experience the same level of improvement in glucose tolerance.

Both male and female obese mice experienced reduced body mass and adiposity with angiotensin-(1-7) treatment, suggesting its potential as a therapeutic target for obesity-related insulin resistance, particularly in females.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sex differences in metabolic effects of angiotensin-(1-7) treatment in obese mice. White, MC., Miller, AJ., Loloi, J., et al.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

Angiotensin 1-7: a peptide for preventing and treating metabolic syndrome. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Is there a rationale for angiotensin blockade in the management of obesity hypertension? [2016]

3. United Arab Emirates pubmed.ncbi.nlm.nih.gov

The role of angiotensin in obesity and metabolic disease. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Possible involvement of the adipose tissue renin-angiotensin system in the pathophysiology of obesity and obesity-related disorders. [2019]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Hemodynamic and metabolic responses to interstitial angiotensin II in normal weight and obese men. [2006]

6. Japan pubmed.ncbi.nlm.nih.gov

Angiotensin-(1-7) protects cardiomyocytes against high glucose-induced injuries through inhibiting reactive oxygen species-activated leptin-p38 mitogen-activated protein kinase/extracellular signal-regulated protein kinase 1/2 pathways, but not the leptin-c-Jun N-terminal kinase pathway in vitro. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Obesity is Associated with Higher Blood Pressure and Higher Levels of Angiotensin II but Lower Angiotensin-(1-7) in Adolescents Born Preterm. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Vascular Actions of Angiotensin 1-7 in the Human Microcirculation: Novel Role for Telomerase. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Differential effects of Mas receptor deficiency on cardiac function and blood pressure in obese male and female mice. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Sex differences in metabolic effects of angiotensin-(1-7) treatment in obese mice. [2020]