LY3971297 for Obesity
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Eli Lilly and Company
Trial Summary
What is the purpose of this trial?This trial is testing a new drug called LY3971297, which is given as an injection under the skin. The study includes both healthy people and obese people with high blood pressure. Researchers will take blood samples to see how much of the drug enters the bloodstream and how long it stays in the body.
Is the drug LY3971297 a promising treatment for obesity?Yes, LY3971297, also known as Long-Acting Atrial Natriuretic Peptide, shows promise as a treatment for obesity. It helps reduce body weight and fat, and it may improve heart health by reducing heart rate and supporting better sodium balance in the body.13467
What safety data is available for LY3971297 (LA-ANP) in treating obesity?The provided research does not directly address the safety data for LY3971297 (LA-ANP) in treating obesity. The studies focus on the relationship between atrial natriuretic peptide (ANP) levels and obesity, as well as the effects of ANP in various contexts, such as weight loss, glucose challenges, and low-calorie diets. However, they do not provide specific safety data for LY3971297 or its use in clinical trials for obesity.25678
What data supports the idea that LY3971297 for Obesity is an effective treatment?The available research shows that atrial natriuretic peptide (ANP), which is related to LY3971297, is linked to changes in body weight and fat. In one study, weight loss in obese rats led to increased levels of ANP, which helped reduce body fat and improve heart health. This suggests that LY3971297 might help with weight loss by increasing ANP levels. However, the studies mainly focus on the relationship between ANP and obesity, rather than directly testing LY3971297, so more research is needed to confirm its effectiveness as a treatment for obesity.15679
Do I have to stop taking my current medications for the trial?The protocol does not specify if you must stop all current medications. However, for Part D, you must have a stable dose of antihypertensive medications for the past 3 months. For Part G, you can continue stable treatments for hypertension, type 2 diabetes, dyslipidemia, and hypothyroidism. Some medications like phosphodiesterase 5 inhibitors, long-acting nitrates, nitric oxide donors, and beta blockers are not allowed for Parts D and G.
Eligibility Criteria
This trial is for healthy individuals or those with obesity and high blood pressure. Healthy participants should have a BMI of 18.5 to 35 kg/m2, while obese participants need a BMI of 30 to 40 kg/m2 and meet specific waist measurements. Certain parts require Chinese or Japanese descent. Participants must not have significant health issues, psychiatric disorders, risky blood pressures, recent large blood donations, heavy nicotine or alcohol use, nor take certain medications.Inclusion Criteria
I am a man who agrees to follow contraception rules or a woman who cannot become pregnant.
Exclusion Criteria
I am using or plan to use long-acting nitrates or nitric oxide donors.
I have a history of or currently have heart, lung, liver, kidney, stomach, hormone, blood, or nerve disorders.
I have been diagnosed with a significant drop in blood pressure upon standing.
Treatment Details
The study tests LY3971297 injections in different groups: healthy people and those with obesity plus high BP. It checks the drug's safety profile by observing side effects and measures how it's absorbed and cleared from the body over approximately two to three months.
8Treatment groups
Experimental Treatment
Placebo Group
Group I: LY3971297 (Part G)Experimental Treatment1 Intervention
Multiple doses of LY3971297 administered SC in participants with decreased estimated glomerular filtration rate (eGFR)
Group II: LY3971297 (Part F)Experimental Treatment1 Intervention
Single doses of LY3971297 administered intravenously (IV) in healthy participants
Group III: LY3971297 (Part E)Experimental Treatment1 Intervention
Multiple doses of LY3971297 administered SC in healthy Japanese participants
Group IV: LY3971297 (Part D)Experimental Treatment1 Intervention
Multiple ascending doses of LY3971297 administered SC in participants with obesity and hypertension
Group V: LY3971297 (Part C)Experimental Treatment1 Intervention
Multiple ascending doses of LY3971297 administered SC in healthy Chinese participants
Group VI: LY3971297 (Part B)Experimental Treatment1 Intervention
Multiple ascending doses of LY3971297 administered SC in healthy participants
Group VII: LY3971297 (Part A)Experimental Treatment1 Intervention
Single ascending doses of LY3971297 administered subcutaneously (SC) in healthy participants
Group VIII: Placebo (Part A, B, C, D, E, & G)Placebo Group1 Intervention
Placebo administered SC
Find a clinic near you
Research locations nearbySelect from list below to view details:
ICON Early Phase ServicesSan Antonio, TX
CenExel ACTAnaheim, CA
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Who is running the clinical trial?
Eli Lilly and CompanyLead Sponsor
References
Effect of experimental obesity and subsequent weight reduction upon circulating atrial natriuretic peptide. [2020]The effect of obesity and weight reduction upon circulating concentrations of atrial natriuretic peptide was assessed in an experimental model of the disease. Obese rats weighing in excess of 750 g were compared with formerly obese animals subjected to a 15-week period of caloric restriction resulting in a 40% reduction in body weight. Mean adipocyte size was significantly reduced with weight loss, as was estimated body fat. Mean arterial blood pressure remained normotensive for both groups, but a significant reduction in heart rate was associated with weight reduction. Circulating atrial natriuretic peptide was significantly elevated in the lean rats, which also exhibited decreased plasma renin activity and a negative sodium balance. Analysis of heart to body weight ratios implied that an obesity-associated, volume-induced cardiac hypertrophy remained even after the normalization of body fat. These results suggest that the diuresis and natriuresis accompanying weight reduction may be facilitated by atrial natriuretic peptide, which was elevated in part due to a persistent left ventricular hypertrophy following the transition from the obese to lean condition.
Low calorie diet enhances renal, hemodynamic, and humoral effects of exogenous atrial natriuretic peptide in obese hypertensives. [2019]The expression of the natriuretic peptide clearance receptor is abundant in human and rat adipose tissue, where it is specifically inhibited by fasting. In obese hypertensives, plasma atrial natriuretic peptide (ANP) levels were found to be lower than in obese normotensives. Therefore, the increased adipose mass might influence ANP levels and/or its biological activity. The aim of the present study was to evaluate whether the humoral, hemodynamic, and renal effects of exogenous ANP in obese hypertensives might be enhanced by a very low calorie diet. Eight obese hypertensives received a bolus injection of ANP (0.6 mg/kg) after 2 weeks of a normal calorie/normal sodium diet, and blood pressure (BP), heart rate, ANP, cGMP, plasma renin activity, and aldosterone were evaluated for 2 hours before and after the injection. Diuresis and natriuresis were measured every 30 minutes. The patients then started a low calorie/normal sodium diet (510 kcal/150 mmol/d) for 4 days, and then the ANP injection protocol was repeated. The low calorie diet induced a slight weight loss (from 90.6+/-1.1 to 87. 7+/-1.2 kg; P
Natriuretic peptides as markers of preclinical cardiac disease in obesity. [2015]Aim of the study was to evaluate the role of atrial (ANP) and brain natriuretic peptides (BNP) as markers of preclinical cardiac disease in obesity.
Obese patients have lower B-type and atrial natriuretic peptide levels compared with nonobese. [2019]Obesity is a risk factor for the development of heart failure, but the causal mechanism remains unclear. Impaired production or enhanced clearance of natriuretic peptides, which regulate sodium balance and sympathetic activation, may play an important role. The authors investigated the relationship of plasma B-type natriuretic peptide and atrial natriuretic peptide levels to body mass index in 100 patients referred for left heart catheterization. Hemodynamic and echocardiographic data were obtained for all study participants. Atrial natriuretic peptide and B-type natriuretic peptide levels were compared in obese (body mass index > or = 30 kg/m2) and nonobese (body mass index
Differential response of the natriuretic peptide system to weight loss and exercise in overweight or obese patients. [2018]Relative atrial natriuretic peptide (ANP) deficiency has been implicated in the pathogenesis of obesity-associated cardiovascular and metabolic disease. We tested the hypothesis that more than 5% body weight reduction through 6 months hypocaloric dieting alters ANP release at rest and more so during exercise in overweight or obese patients.
Plasma proANP1-98 levels are positively associated with central obesity: A cross-sectional study in a general population of China. [2018]Label="BACKGROUND" NlmCategory="BACKGROUND">Atrial natriuretic peptide (ANP) and its prohormone activating enzyme are associated with central obesity, suggesting there may be a potential relationship between proANP1-98 and central obesity. However, the association is still lack of population-based evidence. We explored the association in a general population of China.
Processing-independent proANP measurement for low concentrations in plasma: reference intervals and effect of body mass index and plasma glucose. [2017]Decreased concentrations of pro-atrial-derived natriuretic peptides (proABP) in plasma have been associated with obesity and suggested as a predictor of type 2 diabetes. However, assays for measuring proANP are generally aimed to quantitate higher concentrations of proANP associated with cardiac disease. Therefore, we aimed to measure plasma proANP concentrations in a non-obese Scandinavian reference material and evaluate potential associations of plasma proANP with body mass index (BMI) and plasma glucose, respectively.
Serum proatrial natriuretic peptide concentrations during oral glucose-induced acute hyperinsulinemia in lean and obese men. [2019]Atrial natriuretic peptide (ANP) is primarily seen as a hormone involved in salt and water homeostasis and blood pressure regulation. Evidence supports a link between metabolism and ANP. Circulating ANP concentrations are low in obese individuals with insulin resistance and hyperinsulinemia. The dynamic relationship between insulin and ANP has been sparsely studied. We therefore measured circulating concentrations of midregional proatrial natriuretic peptide (MR-proANP), a stable marker of ANP secretion, and insulin in lean and obese men during an oral glucose challenge. One hundred and three obese men (body mass index (BMI) ≥30.0 kg/m2) were compared with 27 lean men (BMI = 20.0-24.9 kg/m2). During a 75 g oral glucose challenge, circulating concentrations of MR-proANP and insulin were measured at baseline and every half hour for 2 h. Fasting MR-proANP concentrations were lower in the obese men as compared with the lean men (median (interquartile range): 51.2 (38.7-64.7) pmol/L vs. 69.3 (54.3-82.9) pmol/L, P = 0.002). During the oral glucose challenge, serum MR-proANP concentrations fell steadily in the obese men (P < 0.0001), whereas there was no significant fall in the lean men (P = 0.14). However, the time-course curves of MR-proANP did not display a clear reciprocal relation to the time-course curves of insulin. Adjusted for age, the area under curve (AUC) for MR-proANP was inversely correlated with AUC for insulin (r = -0.38, P < 0.0001). In conclusion, during an oral glucose challenge, serum MR-proANP concentrations drop significantly in obese individuals, but the time-course curves of MR-proANP do not display a reciprocal relationship to the time-course curves of insulin.
Clinical effect of obesity on N-terminal pro-B-type natriuretic peptide cut-off concentrations for the diagnosis of acute heart failure. [2023]Obese patients have lower natriuretic peptide concentrations. We hypothesized that adjusting the concentration of N-terminal pro-B-type natriuretic peptide (NT-proBNP) for obesity could further increase its clinical utility in the early diagnosis of acute heart failure (AHF).