Epinephrine + Somatostatin for Obesity

Overseen By Kelli Lytle, PhD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Mayo Clinic

Must not be taking: Statins, Niacin, Fibrates, others

Disqualifiers: Diabetes, Heart disease, Smoking, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a new combination of epinephrine (adrenaline) and somatostatin affects fat tissue, particularly in adults with excess belly fat. Researchers aim to understand why people with different body types store and respond to fat differently. The study includes two groups: one with upper body obesity and another with normal weight, both receiving the same treatment. It is ideal for those struggling with upper body obesity, especially significant belly fat. Participants should not have diabetes or certain heart conditions and must not smoke.

As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial requires you to stop taking certain medications that alter fat metabolism or could interact with the study drugs. If you're on statins, you need to stop them for 4 weeks and get approval from your primary care provider.

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

Research has shown that both epinephrine and somatostatin have been studied in various medical contexts. Epinephrine, a hormone and chemical messenger, is often used in emergencies, such as treating severe allergic reactions. Somatostatin, a hormone that regulates other hormones, treats some hormone-related conditions.

While specific studies on using epinephrine and somatostatin together for obesity are lacking, some information exists on their individual effects. Epinephrine is generally safe when used correctly but can cause side effects like a faster heartbeat. Somatostatin can help manage growth hormone levels but might lead to digestive issues.

This study is in its early stages and primarily examines how the body responds to these two substances together. As a result, detailed safety information about this specific combination is not yet available. Understanding the usual side effects of each provides some expectations, but direct data on their combined effects is still being gathered. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using epinephrine and somatostatin for obesity because they target the body's metabolic processes in a new way. Unlike standard treatments that typically focus on diet, exercise, or medications that reduce appetite or absorption of fat, this combination works by regulating hormones that influence metabolism and fat storage. Epinephrine can boost metabolism and increase energy expenditure, while somatostatin helps to regulate hormone release, potentially leading to a more balanced metabolism. This dual approach could offer a more comprehensive solution to managing obesity, especially for those with upper body obesity.

What evidence suggests that this trial's treatments could be effective for obesity?

This trial will evaluate the combination of epinephrine and somatostatin for their effects on obesity. Research has shown that both epinephrine, also known as adrenaline, and somatostatin play roles in fat processing. Epinephrine aids in breaking down fat, while somatostatin, a hormone, can slow the release of growth hormone, influencing fat storage and usage. Early findings suggest that using these two together might alter fat storage or usage, particularly in individuals with more upper-body fat. However, evidence remains limited on their combined effectiveness for treating obesity. This concept is based on existing knowledge of their effects on fat and hormones. ^{1 2 3 6 7}

Who Is on the Research Team?

Michael D Jensen, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for adults with obesity, particularly those who carry most of their excess weight in the abdominal area. Specific eligibility criteria are not provided, but typically participants would need to meet certain health conditions and agree to follow study procedures.

Inclusion Criteria

I am between 18 and 65, can follow instructions, and am willing to eat specific meals for 3 days.

I have obesity in my upper body or around my organs.

My BMI is between 29.0 and 40.0.

Exclusion Criteria

Allergy to lidocaine

Allergy to indocyanine green

I am not taking medications that affect fat metabolism or cause drug interactions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive infusions of somatostatin and epinephrine to measure stimulated adipose tissue lipolysis

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Epinephrine
• Somatostatin

Trial Overview The study investigates how fat tissue responds differently in people by using two substances: Epinephrin, which can stimulate fat breakdown, and Somatostatin, which may inhibit this process. The goal is to understand why abdominal fat cells behave differently.

How Is the Trial Designed?

Group I: Obesity Group Experimental Treatment 2 Interventions

Subjects that have upper body obesity will receive somatostatin plus epinephrine

Group II: Lean Group Experimental Treatment 2 Interventions

Subject wo are normal weight will receive somatostatin plus epinephrine

Epinephrine is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Epinephrine for:

• Anaphylaxis
• Cardiac arrest
• Severe allergic reactions

Approved in United States as Epinephrine for:

• Anaphylaxis
• Cardiac arrest
• Severe allergic reactions

Approved in Canada as Epinephrine for:

• Anaphylaxis
• Cardiac arrest
• Severe allergic reactions

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

Somatostatin (SRIF) and its related peptides, cortistatins (CST), interact with five cloned SRIF receptors (sst1-5), which play crucial roles in various physiological processes, including the inhibition of growth hormone and other hormone secretions.

Selective receptor targeting is important for therapeutic applications, as certain ligands show high affinity for specific receptors, such as octreotide for sst2/sst5, which can help in managing conditions like tumor growth and hormonal imbalances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug design at peptide receptors: somatostatin receptor ligands. Hannon, JP., Nunn, C., Stolz, B., et al.[2018]

Growth hormone releasing factor (GHRF) significantly stimulates the release of somatostatin (SRIF) from cultured rat hypothalamic cells in a dose-dependent manner, with the highest concentration (10nM) increasing SRIF release by 1.8 times.

The study indicates that calcium is essential for the release of SRIF, as removing calcium from the medium decreased the basal release and inhibited the stimulatory effect of GHRF, suggesting that GHRF may enhance SRIF release in vivo under specific conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The stimulation of somatostatin release by hpGRF44 from rat hypothalamic cells and fragments in vitro. Iwasaki, K., Fujii, A., Merchenthaler, I., et al.[2014]

Synthetic somatostatin (SRIF) effectively inhibits the release of stored rat growth hormone in a dose-dependent manner, with maximal inhibition occurring at 25 nM SRIF, reducing release to 30-40% of basal levels.

Prolonged exposure to SRIF leads to continuous inhibition of growth hormone release, but when SRIF is withdrawn, a rebound effect occurs, indicating that while SRIF can suppress hormone release, it does not result in a net decrease when considering the rebound effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of synthetic somatostatin upon growth hormone release from perifused rat pituitaries. Stachura, ME.[2018]

The synthetic peptide somatostatin effectively inhibits growth hormone release in normal individuals without affecting other hormones like cortisol, prolactin, LH, FSH, or TSH, indicating its specific action on growth hormone regulation.

In patients with acromegaly, somatostatin significantly reduces elevated growth hormone levels while not impacting other anterior-pituitary hormones, but its short biological half-life limits its current therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The effect of synthetic somatostatin in normal and acromegalic males]. Wiegelmann, W., Solbach, HG., Kley, HK., et al.[2013]

Somatostatin (SRIF) is a powerful inhibitor of growth hormone and other peptide releases, acting through high-affinity receptors (sst1-5) that are part of the G protein-coupled receptor family.

A novel nonpeptide compound, NNC 26-9100, was identified as a selective agonist for the sst4 receptor, showing a strong binding affinity (Ki = 6 nM) and potential therapeutic applications in targeting somatostatin receptors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

2-pyridylthioureas: novel nonpeptide somatostatin agonists with SST4 selectivity. Liu, S., Crider, AM., Tang, C., et al.[2018]

Somatostatin plays a complex role in regulating ghrelin levels, acting differently in the brain and periphery; in the brain, it increases ghrelin levels, while in the periphery, it inhibits ghrelin release, particularly after surgery.

The effects of somatostatin on ghrelin are mediated through specific receptor subtypes (sst(2)), highlighting the importance of targeted receptor interactions in understanding hormone regulation and potential therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activation of somatostatin 2 receptors in the brain and the periphery induces opposite changes in circulating ghrelin levels: functional implications. Stengel, A., Taché, Y.[2021]

Somatostatin (SRIH) does not affect the release of adrenocorticotropic hormone (ACTH) under normal conditions but can significantly suppress ACTH release when glucocorticoid feedback is blocked, indicating its role is context-dependent.

SRIH has limited impact on prolactin (PRL) release but can enhance the sensitivity of PRL cells to dopamine, suggesting a complex interaction between these hormones in regulating pituitary function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Studies on the conditions determining the inhibitory effect of somatostatin on adrenocorticotropin, prolactin and thyrotropin release by cultured rat pituitary cells. Lamberts, SW., Zuyderwijk, J., den Holder, F., et al.[2018]

Somatostatin and cortistatin are important peptides that act as neurohormones and neurotransmitters, influencing various biological processes through their interaction with five G protein-coupled receptors (sst1-5).

Recent advancements in mouse models lacking somatostatin ligands or receptors have provided valuable insights into the physiological roles of these peptides, enhancing our understanding of their mechanisms of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Null mutant mouse models of somatostatin and cortistatin, and their receptors. Zeyda, T., Hochgeschwender, U.[2008]

Somatostatin (SRIF) is a neurohormone that inhibits growth hormone secretion and has various roles in the body, acting as a hormone and neuropeptide, with receptors found on several human tumors.

SRIF agonists are clinically used to monitor growth hormone levels in patients with acromegaly, highlighting their therapeutic relevance in managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Somatostatin: a ubiquitous peptide]. Epelbaum, J., Dournaud, P.[2006]

Intracerebroventricular infusion of a somatostatin analogue significantly inhibited the plasma ACTH response to hemorrhage in conscious sheep, demonstrating its potential as a central inhibitor of ACTH release.

The somatostatin analogue completely blocked the increase in plasma ACTH at a higher dose, suggesting that it may work by inhibiting corticotropin-releasing factor release or directly affecting the pituitary gland, although the exact mechanism remains unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracerebroventricular infusion of a cyclic hexapeptide analogue of somatostatin inhibits hemorrhage-induced ACTH release. Wang, XM., Tresham, JJ., Coghlan, JP., et al.[2018]

Somatostatin and its analogs effectively inhibit hormone secretion and can control the growth of various endocrine tumors, highlighting their potential as therapeutic agents.

In vitro studies have revealed the mechanisms by which somatostatin influences tumor proliferation, paving the way for future research into its clinical applications in treating endocrine cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiproliferative effects of somatostatin analogs in endocrine tumours. Zatelli, MC.[2021]

Citations

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Normal Physiology of Growth Hormone in Normal Adults In the present chapter we will briefly review the normal physiology of GH secretion and the effects of GH on intermediary metabolism throughout adulthood.

2. withpower.com withpower.com/trial/early-phase-1-obesity-4-2024-42ac1

Epinephrine + Somatostatin for Obesity This Phase < 1 medical study run by Mayo Clinic is evaluating whether Epinephrine and Somatostatin will have tolerable side effects & efficacy for patients ...

3. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK538498/

Physiology, Endocrine Hormones - StatPearls - NCBI Bookshelf Hormones of the endocrine system are a vast topic with numerous hormones involved, affecting virtually every organ in the human body.

4. mdpi.com mdpi.com/1422-0067/21/7/2568

Role of Somatostatin in the Regulation of Central ... 1. Introduction. Somatostatin (SST), also known as somatotropin release-inhibiting factor, is a growth hormone inhibitory peptide that was first discovered in ...

5. nature.com nature.com/articles/s41392-019-0036-y

Targeting growth hormone function: strategies and ... This review will discuss current and emerging strategies for antagonizing GH function and the potential disease indications.

6. frontiersin.org frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2020.614981/full

A Comparative Update on the Neuroendocrine Regulation ... This review aims for a comparative analysis of our current understanding of the endocrine regulation of GH from the pituitary of vertebrates.

7. sciencedirect.com sciencedirect.com/topics/medicine-and-dentistry/somatomedin

Somatomedin - an overview The IGFs (somatomedins) are a family of peptides that are, in part, GH dependent and mediate many of the anabolic and mitogenic actions of GH.