Effect of Chronotherapy on Blood Pressure - Time of Intake of Blood Pressure Lowering Drugs

August 19, 2024 updated by: Vastra Gotaland Region

Chronotherapy in Hypertension - a Study of Blood Pressure Levels Following Intake of Antihypertensive Medication in the Morning or at Bedtime

A randomized clinical trials with cross-over design to evaluate changes in blood pressure, renal function (creatinine, estimated glomerular filtration), LDL and HDL-cholesterol after taking antihypertensive drugs in the morning or at bedtime. Blood pressure will be estimated by ambulatory blood pressure measurements. There will be a shift in time of drug intake after 8 weeks for each participant. Approximately 100 individuals aged 40-75 years and on stable anti-hypertensive treatment and blood pressure <150/95 mm Hg will be recruited. No new drugs will be introduced during the study.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

High blood pressure (hypertension, HT) is very common and can lead to serious cardiovascular complications and premature death. Despite effective drug treatment many patients do not reach the blood pressure goal. No new antihypertensive drugs have been developed lately, so there is a need for other strategies to increase attainment of goals and diminish the rate of complications. The circadian rhythm can affect sleep, body temperature, hormone levels, metabolism and the effect of drugs. The impact of antihypertensive treatment in the short and long run was described in a large randomized study in primary health care where individuals with hypertension were randomly assigned to take the drugs in the morning or at bedtime. Intake at bedtime resulted in lower blood pressure, better kidney function and lower LDL-cholesterol. Further, after a mean time follow-up of 6 years a 50% reduction of cardiovascular death was seen. There was by time running a difference in antihypertensive drugs and also co-morbidity between the groups. Despite this, there is a need to investigate if chronotherapy might play a role in antihypertensive care.

The aim of the study is to investigate the effect of intake of drugs in the morning compared to at bed-time.

Methods: Patients 40-75 years, will be recruited from two primary health care centers and one clinic of internal medicine. Medical history, current medication will be recorded. Office blood pressure, body height and weight, ECG and ambulatory blood pressure measurement (ABPM) will be performed. Blood will be analyzed for fasting blood glucose, LDL and HDL-cholesterol and creatinine.

After inclusion in the study the patients are randomly, by clinic, allocated to take their antihypertensive drugs in the morning or at bed-time during 8 week. The ordinary medication is used during the study period. The patients are instructed to keep a diary on wake-up and bed-times, side effects, sleep quality and other experiences during therapy. After 8 weeks the investigations at base-line are repeated and a visual analogue scale on sleep, daytime tiredness and urine voiding is recorded. The patients shift to intake of medication on the opposite time of day for 8 weeks. The study is completed with a repeated investigation as above. The analyses of data is performed by researchers of the team that are not aware of the patients' allocation. The diaries will be a base for later in-depth-interviews with a part of the patients. The analyses will be intention-to-treat using appropriate methods for the data. Office blood pressure, blood lipids and kidney function at baseline, 8 and 16 weeks, as well as sleep duration, urine voiding at night will be analyzed. ABPM will be analyzed using mean blood pressure around-the-clock, daytime and nighttime blood pressure, dipping and morning surge.

Study Type

Interventional

Enrollment (Estimated)

120

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Sweden
      • Gothenburg, Sweden
        • Recruiting
        • Sahlgrenska University hospital, Mölndal
        • Contact:
      • Skövde, Sweden, 541 41
        • Recruiting
        • Närhälsan Billingen Primary Health Care Centre
        • Contact:
      • Skövde, Sweden, 541 41
        • Not yet recruiting
        • Närhälsan Norrmalm Primary Health Care Centre
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Diagnosis of hypertension
  • Stable antihypertensive treatment at least 8 weeks prior to inclusion
  • One to four antihypertensive drugs

Exclusion Criteria:

  • Atrial fibrillation/flutter
  • Diabetes
  • Previous stroke or TIA
  • Heart failure
  • Ischemic heart disease
  • Peripheral artery disease
  • Malignant disease with less than one year expected survival
  • Inability to follow study protocol (for instance shift work)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Morning intake
Intake of antihypertensive medication in the morning
Other: Time of ordinary antihypertensive medication intake
Time of ordinary antihypertensive medication intake
Active Comparator: Bedtime intake
Intake of antihypertensive medication at bedtime
Other: Time of ordinary antihypertensive medication intake
Time of ordinary antihypertensive medication intake

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
24 hours blood pressure changes between 8 and 16 weeks.
Time Frame: 8 and 16 weeks
Ambulatory blood pressure changes between 8 and 16 weeks. Systolic and diastolic mean blood pressure level.
8 and 16 weeks
Change of dipping of blood pressure between 8 and 16 weeks.
Time Frame: 8 and 16 weeks
Ratio between daytime and nighttime blood pressure registered after 8 and 16 weeks. Systolic and diastolic mean blood pressure level.
8 and 16 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Daytime blood pressure changes between 8 and 16 weeks.
Time Frame: 8 and 16 weeks
Ambulatory daytime blood pressure registered after 8 and 16 weeks. Systolic and diastolic mean blood pressure level.
8 and 16 weeks
Nighttime blood pressure changes between 8 and 16 weeks.
Time Frame: 8 and 16 weeks
Ambulatory nighttime blood pressure registered after 8 and 16 weeks. Systolic and diastolic mean blood pressure level.
8 and 16 weeks
Office blood pressure changes between 8 and 16 weeks.
Time Frame: 8 and 16 weeks
Office blood pressure registered after 8 and 16 weeks. Systolic and diastolic mean blood pressure level.
8 and 16 weeks
Difference in morning surge of blood pressure between 8 and 16 weeks.
Time Frame: 8 and 16 weeks
Occurrence of morning (yes/no)
8 and 16 weeks
Difference in LDL cholesterol levels between 8 and 16 weeks.
Time Frame: 8 and 16 weeks
LDL cholesterol changes according to time of intake of antihypertensive drugs
8 and 16 weeks
Difference in HDL cholesterol levels between 8 and 16 weeks.
Time Frame: 8 and 16 weeks
HDL cholesterol changes according to time of intake of antihypertensive drugs
8 and 16 weeks
Difference in total cholesterol levels between 8 and 16 weeks.
Time Frame: 8 and 16 weeks
Total cholesterol changes according to time of intake of antihypertensive drugs
8 and 16 weeks
Difference in p-creatinine levels between 8 and 16 weeks.
Time Frame: 8 and 16 weeks
P-creatinine changes according to time of intake of antihypertensive drugs
8 and 16 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Difference in score of Epworth sleepiness scale between 8 and 16 weeks
Time Frame: 8 and 16 weeks
Epworth sleepiness scale score registered by the patients according to time of antihypertensive drug intake
8 and 16 weeks
Perceived side effects 8 weeks
Time Frame: 8 weeks
Perceived side effects registered by the patients (VAS) according to time of antihypertensive drug intake
8 weeks
Perceived side effects 16 weeks
Time Frame: 16 weeks
Perceived side effects registered by the patients (VAS) according to time of antihypertensive drug intake
16 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vastra Gotaland Region

Collaborators

Swedish Heart Lung Foundation

Investigators

  • Principal Investigator: Karin Manhem, Prof, MD, Sahlgrenska University Hospital, Sweden

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 25, 2022

Primary Completion (Estimated)

June 1, 2025

Study Completion (Estimated)

June 1, 2025

Study Registration Dates

First Submitted

April 4, 2022

First Submitted That Met QC Criteria

April 4, 2022

First Posted (Actual)

April 12, 2022

Study Record Updates

Last Update Posted (Actual)

August 20, 2024

Last Update Submitted That Met QC Criteria

August 19, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VGFOUREG-939529

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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