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Treatment of HYpertension: Morning Versus Evening (THYME)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02214498
Recruitment Status : Unknown
Verified August 2014 by Jorie Versmissen, Erasmus Medical Center.
Recruitment status was:  Not yet recruiting
First Posted : August 12, 2014
Last Update Posted : August 15, 2014
Sponsor:
Collaborator:
ZonMw: The Netherlands Organisation for Health Research and Development
Information provided by (Responsible Party):
Jorie Versmissen, Erasmus Medical Center

Brief Summary:

Rationale:

The nocturnal blood pressure mean is an independent and stronger predictor of cardiovascular disease (CVD) risk than either daytime office, awake or 24hour mean blood pressure. In general, when nocturnal blood pressure does not decline CVD risk is higher, usually referred to as "dippers" versus "non-dippers". Evening administration of treatment might lower nocturnal blood pressure more effectively than morning administration, which is most commonly advised.

The main hypothesis of this study is that evening administration of antihypertensive medication might resume the dipping pattern in non-dippers and as a consequence might reduce CVD risk more than morning administration.

Primary objective (in short):

-to prove that evening administration of enalapril/hydrochlorothiazide in non-dippers can resume a dipping blood pressure pattern in non-dippers

Study design: A double-blind placebo-controlled cross-over study Each person will use for one period of six weeks enalapril/hydrochlorothiazide in the morning and placebo in the evening, and one period of six weeks the other way around


Condition or disease Intervention/treatment Phase
Essential Hypertension Drug: Enalapril/hydrochlorothiazide Drug: Placebo Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Treatment of HYpertension: Morning Versus Evening
Study Start Date : May 2015
Estimated Primary Completion Date : May 2017
Estimated Study Completion Date : May 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Enalapril/hydrochlorothiazide
This arm will start with six weeks of administration of enalapril/hydrochlorothiazide in the evening and placebo in the morning, followed by six weeks of active treatment in the morning and placebo in the evening
Drug: Enalapril/hydrochlorothiazide
The intervention implies that morning and evening administration of enalapril/hydrochlorothiazide will be compared
Other Name: To be determined

Drug: Placebo
Placebo Comparator: Placebo
This arm will start with six weeks of morning administration of enalapril/hydrochlorothiazide in the morning and placebo in the evening, followed by six weeks of placebo in the morning and active treatment in the evening
Drug: Enalapril/hydrochlorothiazide
The intervention implies that morning and evening administration of enalapril/hydrochlorothiazide will be compared
Other Name: To be determined

Drug: Placebo



Primary Outcome Measures :
  1. Average nocturnal blood pressure, percentage dipping and nadir of nocturnal blood pressure [ Time Frame: 24 hours ]
    At the end of each treatment period of six weeks, a 24 hour ambulatory blood pressure measurement will be performed


Secondary Outcome Measures :
  1. Percentage of nocturnal diastolic blood pressure measurements below 65 mm hg [ Time Frame: 24 hours ]
    One safety issue on evening administration of antihypertensive treatment is that blood pressure might get too low. We will assess this especially in the dippers.

  2. Urine: Sodium, potassium, protein, melatonin, creatinin [ Time Frame: Two times within 24 hours at the end of six weeks of treatment according to one of the two regimes ]
    Excretion of sodium, potassium, protein and melatonin depend on the circadian clock. Therefore, differences between morning and evening administration of antihypertensive medication are tested

  3. Plasma: enalapril, cortisol, melatonin, aldosterone, ACE activity, gene expression of clock genes [ Time Frame: Moring of 24 hour blood pressure measurement after six weeks of treatment according to a certain regime ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Essential hypertension
  • Stable blood pressure on treatment with Angiotensin Converting Enzyme Inhibitor (ACEI) or Angiotensin II Receptor Blocker (ARB) and hydrochlorothiazide
  • Age between 18 and 85 years
  • WHO performance status 0-1
  • Available for a time period of 15 weeks
  • Written informed consent
  • Dippers: Nocturnal blood pressure fall of 10-20% of daytime values.20
  • Non-dippers: -Nocturnal blood pressure fall of <10% of daytime values

Exclusion Criteria:

  • secondary cause of hypertension
  • use of ARB because of intolerability (e.g. dry cough) of ACEI
  • nocturnal blood pressure fall of >20% or rise
  • renal insufficiency (GFR<60 ml/min)
  • shift work
  • pregnancy or wish to get pregnant
  • use of other antihypertensive medication than ACEI, ARB, hydrochlorothiazide or a calcium channel blocker
  • use of sleeping medication

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02214498


Contacts
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Contact: Jorie Versmissen, MD, PhD j.versmissen@erasmusmc.nl

Locations
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Netherlands
Erasmus MC
Rotterdam, Netherlands
Contact: Jorie Versmissen, MD, PhD       j.versmissen@erasmusmc.nl   
Principal Investigator: Jorie Versmissen, MD, PhD         
Sponsors and Collaborators
Erasmus Medical Center
ZonMw: The Netherlands Organisation for Health Research and Development
Investigators
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Principal Investigator: Jorie Versmissen, MD, PhD Erasmus MC
Study Director: Teun Van Gelder, Prof Erasmus MC
Study Chair: Eric Sijbrands, Prof Erasmus MC

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Responsible Party: Jorie Versmissen, MD, PhD, Erasmus Medical Center
ClinicalTrials.gov Identifier: NCT02214498    
Other Study ID Numbers: 2014_THYME
First Posted: August 12, 2014    Key Record Dates
Last Update Posted: August 15, 2014
Last Verified: August 2014
Keywords provided by Jorie Versmissen, Erasmus Medical Center:
Dipper
Non-dipper
Chronopharmacology
Additional relevant MeSH terms:
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Hypertension
Essential Hypertension
Vascular Diseases
Cardiovascular Diseases
Hydrochlorothiazide
Enalapril
Enalaprilat
Antihypertensive Agents
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Sodium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors