Hypertension, Resistant to Conventional TherapyPhase 1MANP-2NCT04542681
MANP in African Americans With Hypertension
A Phase 1 study testing MANP - 1st Cycle and MANP - 2nd Cycle in people with Hypertension, Resistant to Conventional Therapy, run by Mayo Clinic at 1 site in United States.
Trial summary
Evaluate the cardiovascular properties of MANP in AA with Hypertension Read more about this study
- Who is it for?
- Ages 20 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypertension, Resistant to Conventional Therapy
- What is being tested?
- MANP - 1st Cycle and MANP - 2nd Cycle
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 May 2018to 30 Jun 2023
- 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 20 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Hypertension, defined as a mean supine BP equal to or greater than 140 mmHg and taking at least one standard of care therapies (including a diuretic, angiotensin converting enzyme inhibitor or angiotensin receptor blocker and a calcium channel blocker);
- MDRD estimated GFR > 30 mL/min to be calculated at the screening visit by available serum creatinine
- Male or female African Americans
- Have a body mass index (BMI) within the range of 18-40 kg/m2;
- Be able to communicate effectively with the study personnel
- Be adequately informed of the nature and risks of the study and give written informed consent prior to receiving study medication.
Who cannot join
- Known hypersensitivity or allergy to MANP or other NPs;
- Women of child bearing age
- Having received any investigational drug or device within 30 days prior to entry into the study; 4) A history (within the last 2 years) of alcohol abuse, illicit drug use, significant mental illness, physical dependence to any opioid, or any history of drug 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;
Show all 15Show fewer
- History of CAD, CVD or syncope;
- History of epilepsy or other seizure disorder;
- History of organ transplantation;
- Malignancy within 5 years;
- Clinically significant intrinsic renal disease, renal artery stenosis, or history of fibromuscular dysplasia of the renal arteries and;
- Consumption of a phosphodiesterase-5 inhibitor.
- Known adrenal insufficiency
- 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 while sitting
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I, Single-Blind, Placebo-Controlled Study Evaluating the Cardiovascular Properties of MANP in African Americans With Hypertension
Evaluate the cardiovascular properties of MANP in AA with Hypertension
Read the detailed description
The study is designed in 2 cycles.
Cycle 1 will incorporate 20 participants and include a screening / enrollment visit and 1 study visit. The study visit will be 30 hours and involves SQ administration of placebo (n=10) or MANP 2.5 ug/kg (n=10). Cycle 2 will incorporate 10 participants and include a screening / enrollment visit and 1 study visit. The study visit will be 30 hours and involves SQ administration of MANP 5 ug/kg (n=10). Studies will be performed at either the CRU of Mayo Clinic's CCaTS in Rochester, Minnesota or the University of Mississippi CRU in Jackson, Mississippi.
All participants will have a screening / enrollment visit where a medical history will be obtained and physical examination performed. At this visit informed consent will also be obtained. Hypertension validation as described above will follow. Once hypertension is validated, subjects will be scheduled for the study visit where either placebo or MANP will be administered at Mayo Clinic's or the University of Mississippi's CRU. Three days prior to the study visit, subjects will be initiated on a moderate sodium (3.0g/day) diet. Fluid intake will be restricted to 2.5 liters per day for all subjects. A 24-hour urine sodium collection will be obtained on the 24 hours prior to the study visit to establish adherence to the low sodium diet. Subjects will be maintained on their standard anti-HTN treatment for the entire duration of the study. At the study visit, subjects will be admitted at 07:00 to the CRU fasting. For safety purposes, all subjects will remain in the CRU a total of 24 hours following dosing. The study will be single blind.
Cycle 1:
At the study visit, either SQ placebo (n=10) or SQ MANP 2.5 ug/kg (n=10) will be administered.
Subjects will also be admitted at 07:00 to the CRU in the fasting state. Subjects will take their usual antihypertensive medications in the CRU at time "0 minutes". Over the next 60 minutes, blood pressure, heart rate, renal clearance, neurohumoral and cGMP assessment will be performed as outlined in Table 2. Ninety minutes after administration of the participant's usual antihypertensive medications, SQ placebo or SQ MANP will be administered if the systolic blood pressure is ≥ 120 mm Hg. Blood pressure and heart rate will be measured before and at several intervals after SQ placebo or SQ MANP administration. Four clearances of 6 hrs for total of 24 hrs after the dosing will be performed. At the end of each clearance, the patients will be asked to drink an amount of water equivalent to the sum of blood losses and urinary volume. During each clearance, urinary, hormonal, and hemodynamic measurements will be obtained and averaged for analysis. Subjects will be discharged from the CRU 24 hours after SQ placebo or SQ MANP administration.
If ≤2 study participants who received SQ MANP 2.5 μg/kg experience any of the adverse events listed below then cycle 2 will be initiated. If >2 study participants who received SQ MANP 2.5 μg/kg MANP experience one of the above events then the study will be terminated and we will not proceed to cycle 2.
- Clinically significant hypotension, defined as a decrease from baseline in clinical SBP ≥ 30 mmHg, or a decrease in sitting SBP to < 90 mmHg, or lightheadedness or dizziness or visual symptoms for 5 minutes.
- Any other safety results or adverse experiences that, in the opinion of the investigator, raise concerns about the safety or tolerability of a higher dose.
Cycle 2:
Cycle 2 will commence only if subjects in cycle 1 tolerated SQ MANP 2.5 μg/kg without clinically significant hypotension or other adverse events (as defined above).
In cycle 2, SQ MANP 5 ug/kg (n=10) will be administered at the study visit.
Subjects will also be admitted at 07:00 to the CRU in the fasting state. Subjects will take their usual antihypertensive medications in the CRU at time "0 minutes". Over the next 60 minutes, blood pressure, heart rate, renal clearance, neurohumoral and cGMP assessment will be performed as outlined in Table 2. Ninety minutes after administration of the participant's usual antihypertensive medications, SQ MANP will be administered if the systolic blood pressure is ≥ 120 mm Hg. Blood pressure and heart rate will be measured before and at several intervals after SQ placebo or SQ MANP administration. Four clearances of 6 hrs for total of 24 hrs after the dosing will be performed. At the end of each clearance, the patients will be asked to drink an amount of water equivalent to the sum of blood losses and urinary volume. During each clearance, urinary, hormonal, and hemodynamic measurements will be obtained and averaged for analysis. Subjects will be discharged from the CRU 24 hours after SQ placebo or SQ MANP administration.
- Being tested
- Placebo - 1st Cycle, MANP - 1st Cycle, MANP - 2nd Cycle
- Medical subject headings
- Hypertension Resistant to Conventional Therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Placebo - 1st CycleDrug
Also called 0.9% Normal Saline
Subjects will receive a single SQ injection of placebo/normal saline
MANP - 1st CycleDrug
Also called Mutant ANP
Subjects will receive a single SQ injection of MANP at a concentration of 2.5 μg/kg
MANP - 2nd CycleDrug
Also called Mutant ANP
Subjects will receive a single SQ injection of MANP 5 μg/kg concentration.
| Study group | Role | What they receive |
|---|---|---|
| Placebo - 1st Cycle | Placebo comparator | Subjects will receive a single SQ injection of placebo (0.9% normal saline) (n=10) Receives: Drug: Placebo - 1st Cycle |
| MANP - 1st Cycle | Active comparator | Subjects will receive a single SQ injection of 2.5 μg/kg MANP (n=10) Receives: Drug: MANP - 1st Cycle |
| MANP - 2nd Cycle | Active comparator | Subjects will receive a single SQ injection of 5 μg/Kg MANP (n=10) Receives: Drug: MANP - 2nd Cycle |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Blood Pressure
The primary outcome is change in blood pressure 12 hours after MANP or placebo administration compared to the baseline blood pressure. Blood pressure will be measured by an automated arm blood pressure cuff. The unit of measurement is mm Hg. Time frame = 12 hours.
Measured: 12 hours
Secondary outcomes (4)
Urinary cGMP excretion
Urinary cGMP excretion (pmol/min) 12 hours after MANP or placebo administration compared to baseline measurement. Urinary cGMP excretion will be measured by a 30 minute urine collection.
Measured: 12 hours
Urinary sodium excretion
Urinary sodium excretion (mEq/min) 12 hours after MANP or placebo administration compared to baseline measurement. Urinary sodium excretion will be measured by a 30 minute urine collection.
Measured: 12 hours
Glomerular filtration rate
Glomerular filtration rate (ml/min) 12 hours after MANP or placebo administration compared to baseline measurement. GFR describes the flow rate of filtered fluid through the kidney measured in milliliters per minute per 1.73 m^2 of body surface area and will be determined by iothalamate clearance.
Measured: 12 hours
Plasma aldosterone
Plasma aldosterone 12 hours after MANP or placebo administration compared to baseline measurement. Aldosterone is measured by analyzing a blood specimen.
Measured: 12 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2020
- Study start1 May 2018
- Primary completion30 Dec 2022 (estimated)
- Study completion30 Jun 2023 (estimated)
Why it stopped: Study was withdrawn and replaced by a larger study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hypertension, Resistant to Conventional TherapyStudies 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
- Non-randomised
- Intervention model
- Sequential
- Model description
- The study is designed in 2 cycles. The first cycle subjects will receive Placebo (n=10) or MANP 2.5 ug/kg (n=20). In the second cycle subjects will receive MANP 5 ug/kg/ (n=10).
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- 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
- NCT04542681
- Sponsor's protocol ID
- IRB # 17-007947
- Acronym
- MANP-2
- Status last verified
- Mar 2023
- First submitted
- 18 Dec 2018
- Last updated
- 9 Mar 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Single-Blind, Placebo-Controlled Study Evaluating the Cardiovascular Properties of MANP in African Americans With Hypertension
- ClinicalTrials.gov ID
- NCT04542681
- Acronym / sponsor ID
- MANP-2 / IRB # 17-007947
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study was withdrawn and replaced by a larger study
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- 1 May 2018 (actual)
- Primary completion
- 30 Dec 2022 (estimated)
- Study completion
- 30 Jun 2023 (estimated)
- First posted
- 9 Sep 2020 (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 properties of MANP in AA with Hypertension
Detailed description
The study is designed in 2 cycles.
Cycle 1 will incorporate 20 participants and include a screening / enrollment visit and 1 study visit. The study visit will be 30 hours and involves SQ administration of placebo (n=10) or MANP 2.5 ug/kg (n=10). Cycle 2 will incorporate 10 participants and include a screening / enrollment visit and 1 study visit. The study visit will be 30 hours and involves SQ administration of MANP 5 ug/kg (n=10). Studies will be performed at either the CRU of Mayo Clinic's CCaTS in Rochester, Minnesota or the University of Mississippi CRU in Jackson, Mississippi.
All participants will have a screening / enrollment visit where a medical history will be obtained and physical examination performed. At this visit informed consent will also be obtained. Hypertension validation as described above will follow. Once hypertension is validated, subjects will be scheduled for the study visit where either placebo or MANP will be administered at Mayo Clinic's or the University of Mississippi's CRU. Three days prior to the study visit, subjects will be initiated on a moderate sodium (3.0g/day) diet. Fluid intake will be restricted to 2.5 liters per day for all subjects. A 24-hour urine sodium collection will be obtained on the 24 hours prior to the study visit to establish adherence to the low sodium diet. Subjects will be maintained on their standard anti-HTN treatment for the entire duration of the study. At the study visit, subjects will be admitted at 07:00 to the CRU fasting. For safety purposes, all subjects will remain in the CRU a total of 24 hours following dosing. The study will be single blind.
Cycle 1:
At the study visit, either SQ placebo (n=10) or SQ MANP 2.5 ug/kg (n=10) will be administered.
Subjects will also be admitted at 07:00 to the CRU in the fasting state. Subjects will take their usual antihypertensive medications in the CRU at time "0 minutes". Over the next 60 minutes, blood pressure, heart rate, renal clearance, neurohumoral and cGMP assessment will be performed as outlined in Table 2. Ninety minutes after administration of the participant's usual antihypertensive medications, SQ placebo or SQ MANP will be administered if the systolic blood pressure is ≥ 120 mm Hg. Blood pressure and heart rate will be measured before and at several intervals after SQ placebo or SQ MANP administration. Four clearances of 6 hrs for total of 24 hrs after the dosing will be performed. At the end of each clearance, the patients will be asked to drink an amount of water equivalent to the sum of blood losses and urinary volume. During each clearance, urinary, hormonal, and hemodynamic measurements will be obtained and averaged for analysis. Subjects will be discharged from the CRU 24 hours after SQ placebo or SQ MANP administration.
If ≤2 study participants who received SQ MANP 2.5 μg/kg experience any of the adverse events listed below then cycle 2 will be initiated. If >2 study participants who received SQ MANP 2.5 μg/kg MANP experience one of the above events then the study will be terminated and we will not proceed to cycle 2.
- Clinically significant hypotension, defined as a decrease from baseline in clinical SBP ≥ 30 mmHg, or a decrease in sitting SBP to < 90 mmHg, or lightheadedness or dizziness or visual symptoms for 5 minutes.
- Any other safety results or adverse experiences that, in the opinion of the investigator, raise concerns about the safety or tolerability of a higher dose.
Cycle 2:
Cycle 2 will commence only if subjects in cycle 1 tolerated SQ MANP 2.5 μg/kg without clinically significant hypotension or other adverse events (as defined above).
In cycle 2, SQ MANP 5 ug/kg (n=10) will be administered at the study visit.
Subjects will also be admitted at 07:00 to the CRU in the fasting state. Subjects will take their usual antihypertensive medications in the CRU at time "0 minutes". Over the next 60 minutes, blood pressure, heart rate, renal clearance, neurohumoral and cGMP assessment will be performed as outlined in Table 2. Ninety minutes after administration of the participant's usual antihypertensive medications, SQ MANP will be administered if the systolic blood pressure is ≥ 120 mm Hg. Blood pressure and heart rate will be measured before and at several intervals after SQ placebo or SQ MANP administration. Four clearances of 6 hrs for total of 24 hrs after the dosing will be performed. At the end of each clearance, the patients will be asked to drink an amount of water equivalent to the sum of blood losses and urinary volume. During each clearance, urinary, hormonal, and hemodynamic measurements will be obtained and averaged for analysis. Subjects will be discharged from the CRU 24 hours after SQ placebo or SQ MANP administration.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- The study is designed in 2 cycles. The first cycle subjects will receive Placebo (n=10) or MANP 2.5 ug/kg (n=20). In the second cycle subjects will receive MANP 5 ug/kg/ (n=10).
| Arm | Type | Receives |
|---|---|---|
| Placebo - 1st Cycle | Placebo comparator | Drug: Placebo - 1st CycleSubjects will receive a single SQ injection of placebo (0.9% normal saline) (n=10) |
| MANP - 1st Cycle | Active comparator | Drug: MANP - 1st CycleSubjects will receive a single SQ injection of 2.5 μg/kg MANP (n=10) |
| MANP - 2nd Cycle | Active comparator | Drug: MANP - 2nd CycleSubjects will receive a single SQ injection of 5 μg/Kg MANP (n=10) |
Who may qualify
- Ages
- 20 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Hypertension, defined as a mean supine BP equal to or greater than 140 mmHg and taking at least one standard of care therapies (including a diuretic, angiotensin converting enzyme inhibitor or angiotensin receptor blocker and a calcium channel blocker);
- MDRD estimated GFR > 30 mL/min to be calculated at the screening visit by available serum creatinine
- Male or female African Americans
- Have a body mass index (BMI) within the range of 18-40 kg/m2;
- Be able to communicate effectively with the study personnel
Key exclusion criteria (15 listed)
- Known hypersensitivity or allergy to MANP or other NPs;
- Women of child bearing age
- Having received any investigational drug or device within 30 days prior to entry into the study; 4) A history (within the last 2 years) of alcohol abuse, illicit drug use, significant mental illness, physical dependence to any opioid, or any history of drug 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;
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 |
|---|---|---|
| Placebo - 1st CycleAlso: 0.9% Normal SalineSubjects will receive a single SQ injection of placebo/normal saline | Drug | Placebo - 1st Cycle |
| MANP - 1st CycleAlso: Mutant ANPSubjects will receive a single SQ injection of MANP at a concentration of 2.5 μg/kg | Drug | MANP - 1st Cycle |
| MANP - 2nd CycleAlso: Mutant ANPSubjects will receive a single SQ injection of MANP 5 μg/kg concentration. | Drug | MANP - 2nd Cycle |
Primary outcome
Change in Blood Pressure
Time frame: 12 hours
The primary outcome is change in blood pressure 12 hours after MANP or placebo administration compared to the baseline blood pressure. Blood pressure will be measured by an automated arm blood pressure cuff. The unit of measurement is mm Hg. Time frame = 12 hours.
4 secondary outcomes
Urinary cGMP excretion
Time frame: 12 hours
Urinary sodium excretion
Time frame: 12 hours
Glomerular filtration rate
Time frame: 12 hours
Plasma aldosterone
Time frame: 12 hours
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2023.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
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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 - 1st Cycle and MANP - 2nd Cycle in people with Hypertension, Resistant to Conventional Therapy, 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 6 inclusion and 15 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: withdrawn, as of the sponsor's last update on 9 Mar 2023. 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 was withdrawn before enrolling participants, so there are no results.
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?
Change in Blood Pressure (time frame: 12 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Mar 2023.