MANP in Hypertension and Metabolic Syndrome

NCT03781739 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: IRB # 16-005813
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

Evaluate the cardiovascular and metabolic properties of MANP in subjects with HTN and MS according to rs5068 genotypes

Conditions

Hypertension; Metabolic Syndrome

Outcome Measures

Primary Outcomes (3)

• cardiovascular outcome

  systolic blood pressure

  24 hours

• second messenger

  cGMP plasma levels

  24 hours

• metabolic outcome

  glycerol and non-esterified fatty acids (NEFA) plasma levels

  24 hours

Secondary Outcomes (2)

• secondary cardiovascular outcome

  24 hours

• secondary metabolic outcome

  24 hours

Study Arms (2)

MANP

EXPERIMENTAL

subjects receiving MANP (2.5 micrograms/kg, single subcutaneous injection)

Drug: MANP

Placebo

PLACEBO COMPARATOR

subjects receiving placebo (saline solution, single subcutaneous injection)

Drug: MANP

Interventions

MANP DRUG

single subcutaneous injection of MANP and monitoring of metabolic, cardiovascular and renal parameters

MANP; Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Hypertension defined as 140 mmHg ≤ systolic BP ≤ 180 mmHg or 90 mmHg ≤ diastolic BP ≤ 100 mmHg despite anti-hypertensive medical therapy
• Metabolic Syndrome defined as the presence of any two of the following traits:
• Abdominal obesity, defined as a waist circumference in men ≥102 cm (40 in) and in women ≥88 cm (35 in)
• Serum triglycerides ≥150 mg/dL (1.7 mmol/L)
• Serum HDL cholesterol \<40 mg/dL (1 mmol/L) in men and \<50 mg/dL (1.3 mmol/L) in women or drug treatment for low HDL cholesterol
• Fasting plasma glucose ≥100 mg/dL (5.6 mmol/L) or drug treatment for elevated blood glucose
• Between the ages of 18 and 75 years
• Use of antihypertensive medications at a stable dose for 30 days preceding screening visit.
• Use of statins or ezetimibe or combinations on stable dose for 60 days preceding screening visit.

You may not qualify if:

• Known hypersensitivity or allergy to MANP or its components, carperitide, other natriuretic peptides, or related compounds;
• Subjects with orthostatic hypotension at the screening visit, defined as a decrease in systolic BP of \>20 mmHg or a decrease in diastolic BP of \>10 mmHg within three minutes of standing when compared with blood pressure from the sitting position.
• Subjects with a systolic BP \>180 mmHg or a diastolic BP \>100 mmHg
• Women of child-bearing potential
• The presence of abnormal laboratory values at screening visit considered clinically significant by the Investigator. Specifically they will be excluded if a) Serum sodium of \< 135 mEq/dL or \> 145 mEq/dL; b) Serum potassium of \< 3.5 mEq/dL or \> 5.1 mEq/dL
• Subjects whose body weight has changed more than 3% in the last 3 months
• Having received any investigational drug or device within 30 days prior to entry into the study;
• A history (within the last 2 years) of alcohol risky use (defined as more than 14 standard drinks per week on average or more than 4 drinks on any day for men under age 65 - defined as more than 7 standard drinks per week on average or more than 3 drinks on any day for women and adults 65 years and older);
• A history of illicit drug use, psychiatric illness that might impair the participation to the study, physical dependence to any opioid, or any history of substance abuse or addiction;
• A history of difficulty with donating blood or donated blood or blood products within 45 days prior to enrollment;
• Clinically significant new illness in the 1 month before screening in the opinion of the Investigator;
• History of severe allergies;
• History of coronary artery disease or cerebrovascular disease or syncope;
• History of epilepsy or other seizure disorder;
• History of organ transplantation;

Sponsors & Collaborators

• Mayo Clinic: lead
• American Heart Association: collaborator

Study Sites (1)

Mayo Foundation

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• Ma X, McKie PM, Iyer SR, Scott C, Bailey K, Johnson BK, Benike SL, Chen H, Miller WL, Cabassi A, Burnett JC Jr, Cannone V. MANP in Hypertension With Metabolic Syndrome: Proof-of-Concept Study of Natriuretic Peptide-Based Therapy for Cardiometabolic Disease. JACC Basic Transl Sci. 2023 Nov 1;9(1):18-29. doi: 10.1016/j.jacbts.2023.08.011. eCollection 2024 Jan.

  PMID: 38362338 DERIVED

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Hypertension; Metabolic Syndrome

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Paul M McKie, M.D.

  Mayo Foundation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 18, 2018
• First Posted: December 20, 2018
• Study Start: August 18, 2017
• Primary Completion: November 14, 2019
• Study Completion: December 10, 2019
• Last Updated: November 13, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)