MANP in Hypertension and Metabolic Syndrome
Condition: Hypertension; Metabolic Syndrome
MeSH terms: Hypertension; Metabolic Syndrome; Syndrome
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

Intervention name(s): MANP
Intervention type(s): Drug
Intervention description(s): single subcutaneous injection of MANP and monitoring of metabolic, cardiovascular and renal parameters
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment