HypertensionPhase 1MANP-HTN-MSNCT03781739
MANP in Hypertension and Metabolic Syndrome
A Phase 1 study testing MANP in people with Hypertension and Metabolic Syndrome, run by Mayo Clinic at 1 site in United States.
Trial summary
Evaluate the cardiovascular and metabolic properties of MANP in subjects with HTN and MS according to rs5068 genotypes Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hypertension, Metabolic Syndrome
- What is being tested?
- MANP
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Aug 2017to 10 Dec 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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;
- Malignancy within 5 years of the screening visit (with the exception of basal cell and squamous cell skin carcinoma);
- Clinically significant intrinsic renal disease, renal artery stenosis, or history of fibromuscular dysplasia of the renal arteries;
- Consumption of a phosphodiesterase-5 inhibitor (sildenafil, vardenafil, or tadalafil) within 72 hours of receiving MANP.
- Episodic or chronic use of nitrates (Isordil, nitroglycerine), MAO inhibitors, antipsychotics, antiarrhythmics, psychostimulants, systemic corticosteroids, cholestyramine and cholestipol reisins, fibrates, nicotinic acid, cyclosporin, rifampin or other highly potent PgP inhibitors.
- Any disease or condition (medical or surgical) which, in the opinion of the investigator, might compromise the hematologic, cardiovascular, pulmonary, renal, gastrointestinal, hepatic, or central nervous system; or other conditions that may interfere with the absorption, distribution, metabolism or excretion of study drug, or would place the subject at increased risk.
- Subjects who smoke or have any history of tobacco product use more recently than 6 months prior to the enrollment into the study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A PHASE I, DOUBLE BLIND, PLACEBO-CONTROLLED STUDY EVALUATING THE CARDIOVASCULAR AND METABOLIC PROPERTIES OF MANP IN SUBJECTS WITH HYPERTENSION AND METABOLIC SYNDROME ACCORDING TO RS5068 GENOTYPES
Evaluate the cardiovascular and metabolic properties of MANP in subjects with HTN and MS according to rs5068 genotypes
Read the detailed description
6 Study Procedures 6.1 Day 0 - Visit 1 (screening visit) 6.2 At visit 1 informed consent will be obtained (Table 1). Introduction and orientation to the study will take place. Medical history will be collected. Physical exam will be performed and laboratory exams history will be screened. Electrocardiogram will be recorded and screening laboratory tests will be performed. Blood pressure and heart rate will be recorded. Subjects will be instructed about the fluid intake allowed (2.5 liter/day) and the diet (moderate sodium intake: 3.0 gr/day) to follow for the duration of the study from day 1 to day 7. Subjects will be instructed on completing a 24-hour urine collection starting on day 4 at 4pm (see day 4 below). Antihypertensive medications are required to be at a stable dose for 30 days preceding visit 1 on day 1. Throughout the duration of the study subjects will be maintained on their chronic antihypertensive treatment except for day 6 in which MANP or placebo will be administered. Subjects will be instructed to avoid strenuous physical activities and to abstain from smoking and alcohol from day 1 until the completion of the study on day 7. Caffeine consumption will be prohibited from 7.00 pm on day 5 until the dismissal from the CRTU on day 7. Day 1 Start of diet and fluid restriction compliance. (Interval of time between day 0 and day 1 will depend upon the CRTU schedules 6.3 Day 4 On Day 4 at 4 pm the subjects will start 24-hour urine collection in order to establish adherence to the moderate sodium diet (Table 1).
6.4 Day 5 On day 5 at 4pm subjects will bring the 24-hour urine collection to the CRTU and 24-hour urine sodium will be measured. If the patient has been compliant with the sodium diet, she/he will be admitted to the CRTU to continue the study and a physical exam will be performed. At 7.00 pm subjects will start fasting and abstain from their usual hypoglycemic therapy in consideration of the blood draws for metabolic parameters that will be performed on day 6. Caffeine consumption is prohibited from 7:00 pm on day 5 until the dismissal from the CRTU on day 7.
6.5 Day 6 - Visit 2 On day 6 at 8:00 am enrolled patients will receive a single injection of MANP (2.5 μg/kg SQ) or placebo (0.9% saline solution) and will be under observation for the 24 hours following the MANP/placebo administration (Table 1). Blood pressure and heart rate will be monitored continually and recorded before MANP/placebo injection and at several intervals after MANP/placebo administration. Timed urine collection and blood samples to evaluate neurohumoral, renal function and metabolic plasma parameters will be collected prior to MANP /placebo injection and at different time points after MANP and placebo administration. Subjects will eat their meal and take their usual hypoglycemic medications after the last blood draw for metabolic parameters (4 hours after the MANP injection). Subjects will be maintained on their chronic antihypertensive treatment except for day 6 in which MANP will be administered. They will take their usual antihypertensive therapy 24 hours after MANP injection.
6.6 Day 7 Once completed the 24 hour observation following MANP administration a physical exam will be performed and the subjects will be dismissed from the CRTU
6.7 Day 14 (± 2 days) Laboratory tests will be performed and assessed. Subjects will be contacted by phone to review laboratory tests results and assess the onset of any potential side effect following the MANP/placebo administration.
6.8 Day 30 (-2 days, + 5 days) Blood collection for anti-MANP antibody testing will be performed.
- Conditions
- Hypertension, Metabolic Syndrome
- Being tested
- MANP
- Medical subject headings
- Hypertension, Metabolic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MANPDrug
single subcutaneous injection of MANP and monitoring of metabolic, cardiovascular and renal parameters
| Study group | Role | What they receive |
|---|---|---|
| MANP | Experimental | subjects receiving MANP (2.5 micrograms/kg, single subcutaneous injection) Receives: Drug: MANP |
| Placebo | Placebo comparator | subjects receiving placebo (saline solution, single subcutaneous injection) Receives: Drug: MANP |
What is being measured
The primary outcome is the main question the study is designed to answer.
cardiovascular outcome
systolic blood pressure
Measured: 24 hours
second messenger
cGMP plasma levels
Measured: 24 hours
metabolic outcome
glycerol and non-esterified fatty acids (NEFA) plasma levels
Measured: 24 hours
Secondary outcomes (2)
secondary cardiovascular outcome
diastolic blood pressure
Measured: 24 hours
secondary metabolic outcome
adiponectin plasma levels
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2018
- Study start18 Aug 2017
- Primary completion14 Nov 2019
- Study completion10 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HypertensionStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- American Heart Association
- Responsible party
- Principal investigator, Paul M. McKie, M.D., Mayo Clinic
- Investigators
- Paul M McKie, M.D., Principal investigator, Mayo Foundation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03781739
- Sponsor's protocol ID
- IRB # 16-005813
- Acronym
- MANP-HTN-MS
- Status last verified
- Nov 2020
- First submitted
- 18 Dec 2018
- Last updated
- 13 Nov 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 38362338
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A PHASE I, DOUBLE BLIND, PLACEBO-CONTROLLED STUDY EVALUATING THE CARDIOVASCULAR AND METABOLIC PROPERTIES OF MANP IN SUBJECTS WITH HYPERTENSION AND METABOLIC SYNDROME ACCORDING TO RS5068 GENOTYPES
- ClinicalTrials.gov ID
- NCT03781739
- Acronym / sponsor ID
- MANP-HTN-MS / IRB # 16-005813
- Conditions
- Hypertension, Metabolic Syndrome
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- American Heart Association
- Study start
- 18 Aug 2017 (actual)
- Primary completion
- 14 Nov 2019 (actual)
- Study completion
- 10 Dec 2019 (actual)
- First posted
- 20 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Evaluate the cardiovascular and metabolic properties of MANP in subjects with HTN and MS according to rs5068 genotypes
Detailed description
6 Study Procedures 6.1 Day 0 - Visit 1 (screening visit) 6.2 At visit 1 informed consent will be obtained (Table 1). Introduction and orientation to the study will take place. Medical history will be collected. Physical exam will be performed and laboratory exams history will be screened. Electrocardiogram will be recorded and screening laboratory tests will be performed. Blood pressure and heart rate will be recorded. Subjects will be instructed about the fluid intake allowed (2.5 liter/day) and the diet (moderate sodium intake: 3.0 gr/day) to follow for the duration of the study from day 1 to day 7. Subjects will be instructed on completing a 24-hour urine collection starting on day 4 at 4pm (see day 4 below). Antihypertensive medications are required to be at a stable dose for 30 days preceding visit 1 on day 1. Throughout the duration of the study subjects will be maintained on their chronic antihypertensive treatment except for day 6 in which MANP or placebo will be administered. Subjects will be instructed to avoid strenuous physical activities and to abstain from smoking and alcohol from day 1 until the completion of the study on day 7. Caffeine consumption will be prohibited from 7.00 pm on day 5 until the dismissal from the CRTU on day 7. Day 1 Start of diet and fluid restriction compliance. (Interval of time between day 0 and day 1 will depend upon the CRTU schedules 6.3 Day 4 On Day 4 at 4 pm the subjects will start 24-hour urine collection in order to establish adherence to the moderate sodium diet (Table 1).
6.4 Day 5 On day 5 at 4pm subjects will bring the 24-hour urine collection to the CRTU and 24-hour urine sodium will be measured. If the patient has been compliant with the sodium diet, she/he will be admitted to the CRTU to continue the study and a physical exam will be performed. At 7.00 pm subjects will start fasting and abstain from their usual hypoglycemic therapy in consideration of the blood draws for metabolic parameters that will be performed on day 6. Caffeine consumption is prohibited from 7:00 pm on day 5 until the dismissal from the CRTU on day 7.
6.5 Day 6 - Visit 2 On day 6 at 8:00 am enrolled patients will receive a single injection of MANP (2.5 μg/kg SQ) or placebo (0.9% saline solution) and will be under observation for the 24 hours following the MANP/placebo administration (Table 1). Blood pressure and heart rate will be monitored continually and recorded before MANP/placebo injection and at several intervals after MANP/placebo administration. Timed urine collection and blood samples to evaluate neurohumoral, renal function and metabolic plasma parameters will be collected prior to MANP /placebo injection and at different time points after MANP and placebo administration. Subjects will eat their meal and take their usual hypoglycemic medications after the last blood draw for metabolic parameters (4 hours after the MANP injection). Subjects will be maintained on their chronic antihypertensive treatment except for day 6 in which MANP will be administered. They will take their usual antihypertensive therapy 24 hours after MANP injection.
6.6 Day 7 Once completed the 24 hour observation following MANP administration a physical exam will be performed and the subjects will be dismissed from the CRTU
6.7 Day 14 (± 2 days) Laboratory tests will be performed and assessed. Subjects will be contacted by phone to review laboratory tests results and assess the onset of any potential side effect following the MANP/placebo administration.
6.8 Day 30 (-2 days, + 5 days) Blood collection for anti-MANP antibody testing will be performed.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MANP | Experimental | Drug: MANPsubjects receiving MANP (2.5 micrograms/kg, single subcutaneous injection) |
| Placebo | Placebo comparator | Drug: MANPsubjects receiving placebo (saline solution, single subcutaneous injection) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MANPsingle subcutaneous injection of MANP and monitoring of metabolic, cardiovascular and renal parameters | Drug | MANP, Placebo |
Primary outcome
cardiovascular outcome
Time frame: 24 hours
systolic blood pressure
second messenger
Time frame: 24 hours
cGMP plasma levels
metabolic outcome
Time frame: 24 hours
glycerol and non-esterified fatty acids (NEFA) plasma levels
2 secondary outcomes
secondary cardiovascular outcome
Time frame: 24 hours
secondary metabolic outcome
Time frame: 24 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2020.
- Derived from this study: PubMed 38362338Ma 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.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul M McKie, M.D. principal investigator
Mayo Foundation
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MANP in people with Hypertension and Metabolic Syndrome, run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
cardiovascular outcome (time frame: 24 hours). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03781739, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2020.