Epinephrine + Somatostatin for Obesity

Recruiting in Palo Alto (17 mi)

Overseen by Michael D Jensen, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: Mayo Clinic

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

Disqualifiers: Diabetes, Heart disease, Smoking, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

Adults who gain most of their excess weight in the abdominal area typically do not respond to factors that "turn on" fat cells the same way as people who don't have excessive weight. Researchers are trying to understand why fat tissue responds differently in people with different body types.

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.

What data supports the effectiveness of the drug Epinephrine + Somatostatin for Obesity?

Somatostatin, a component of the treatment, is known to inhibit the release of growth hormone and other peptides, which may help regulate body functions related to obesity. Additionally, somatostatin analogs have shown potential in controlling hormone secretion and tumor growth in endocrine conditions, suggesting possible benefits in managing obesity-related hormonal imbalances. ^{1 2 3 4 5}

Is the combination of Epinephrine and Somatostatin safe for human use?

The research articles reviewed do not provide specific safety data for the combination of Epinephrine and Somatostatin in humans. However, Somatostatin has been studied for its effects on hormone release and is used in clinical settings for other conditions, suggesting it has been evaluated for safety in those contexts. ^{4 6 7 8 9}

How is the drug Epinephrine + Somatostatin unique for treating obesity?

The combination of Epinephrine and Somatostatin for obesity is unique because it leverages Somatostatin's ability to inhibit hormone release, including growth hormone and ghrelin, which are involved in appetite and metabolism regulation. This dual action could potentially offer a novel approach to managing obesity by targeting both central and peripheral pathways that influence weight gain. ^{2 3 4 10 11}

Research Team

Michael D Jensen, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Epinephrine (Hormone Therapy)
• Somatostatin (Hormone Therapy)

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.

Participant Groups

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 Canada for the following indications:

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+

Dr. Gianrico Farrugia

Mayo Clinic

Chief Executive Officer since 2019

MD from University of Malta Medical School

Dr. Richard Afable

Mayo Clinic

Chief Medical Officer

MD from Loyola Stritch School of Medicine

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

Collaborator

Trials

2,513

Recruited

4,366,000+

Dr. Griffin P. Rodgers

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

Chief Executive Officer since 2007

MD, M.A.C.P.

Dr. Griffin P. Rodgers

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

Chief Medical Officer since 2007

MD, M.A.C.P.

Findings from Research

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]

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 (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]

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]

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 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 (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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

[The effect of synthetic somatostatin in normal and acromegalic males]. [2013]

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

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

3. Japan pubmed.ncbi.nlm.nih.gov

The stimulation of somatostatin release by hpGRF44 from rat hypothalamic cells and fragments in vitro. [2014]

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

2-pyridylthioureas: novel nonpeptide somatostatin agonists with SST4 selectivity. [2018]

5. England pubmed.ncbi.nlm.nih.gov

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

6. France pubmed.ncbi.nlm.nih.gov

[Somatostatin: a ubiquitous peptide]. [2006]

7. Switzerland 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. [2018]

8. Ireland pubmed.ncbi.nlm.nih.gov

Null mutant mouse models of somatostatin and cortistatin, and their receptors. [2008]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Intracerebroventricular infusion of a cyclic hexapeptide analogue of somatostatin inhibits hemorrhage-induced ACTH release. [2018]

10. Switzerland 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. [2021]

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

Drug design at peptide receptors: somatostatin receptor ligands. [2018]