HypertensionNCT05322967
Effect of Chronotherapy on Blood Pressure - Time of Intake of Blood Pressure Lowering Drugs
A study testing Time of ordinary antihypertensive medication intake in people with Hypertension and Drug Therapy, run by Vastra Gotaland Region at 3 sites in Sweden.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 40 to 75 years
- Conditions the study is for
- Hypertension, Drug Therapy, Primary Health Care
- What is being tested?
- Time of ordinary antihypertensive medication intake
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 3 sitesSweden
- Study dates
- 25 Jun 2022to 1 Jun 2025
- Phase
- Interventional
- 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 40 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of hypertension
- Stable antihypertensive treatment at least 8 weeks prior to inclusion
- One to four antihypertensive drugs
Who cannot join
- 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)
Trial locations and contacts
3 sites in 1 country.
Sweden3 sites, 3 recruiting
- Recruiting
Sahlgrenska University Hospital, Mölndal
Gothenburg
Johan-Emil Bager, PhD, MD, +46739728299, johan-emil.bager@vgregion.se
- Recruiting
Närhälsan Billingen Primary Health Care Centre
Skövde, 541 41
Kristina Bengtsson Boström, +46702409091, kristina.a.bengtsson@vgregion.se
- Not yet recruiting
Närhälsan Norrmalm Primary Health Care Centre
Skövde, 541 41
Tobias Andersson, +46707 143437, tobias.e.andersson@vgregion.se
About this study
Official title: 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.
Read the 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.
- Conditions
- Hypertension, Drug Therapy, Primary Health Care
- Being tested
- Time of ordinary antihypertensive medication intake
- Keywords
- Cross-over study
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Time of ordinary antihypertensive medication intakeOther
Time of ordinary antihypertensive medication intake
| Study group | Role | What they receive |
|---|---|---|
| Morning intake | Active comparator | Intake of antihypertensive medication in the morning Receives: Other: Time of ordinary antihypertensive medication intake |
| Bedtime intake | Active comparator | Intake of antihypertensive medication at bedtime Receives: Other: Time of ordinary antihypertensive medication intake |
What is being measured
The primary outcome is the main question the study is designed to answer.
24 hours blood pressure changes between 8 and 16 weeks.
Ambulatory blood pressure changes between 8 and 16 weeks. Systolic and diastolic mean blood pressure level.
Measured: 8 and 16 weeks
Change of dipping of blood pressure between 8 and 16 weeks.
Ratio between daytime and nighttime blood pressure registered after 8 and 16 weeks. Systolic and diastolic mean blood pressure level.
Measured: 8 and 16 weeks
Secondary outcomes (8)
Daytime blood pressure changes between 8 and 16 weeks.
Ambulatory daytime blood pressure registered after 8 and 16 weeks. Systolic and diastolic mean blood pressure level.
Measured: 8 and 16 weeks
Nighttime blood pressure changes between 8 and 16 weeks.
Ambulatory nighttime blood pressure registered after 8 and 16 weeks. Systolic and diastolic mean blood pressure level.
Measured: 8 and 16 weeks
Office blood pressure changes between 8 and 16 weeks.
Office blood pressure registered after 8 and 16 weeks. Systolic and diastolic mean blood pressure level.
Measured: 8 and 16 weeks
Difference in morning surge of blood pressure between 8 and 16 weeks.
Occurrence of morning (yes/no)
Measured: 8 and 16 weeks
Difference in LDL cholesterol levels between 8 and 16 weeks.
LDL cholesterol changes according to time of intake of antihypertensive drugs
Measured: 8 and 16 weeks
Difference in HDL cholesterol levels between 8 and 16 weeks.
HDL cholesterol changes according to time of intake of antihypertensive drugs
Measured: 8 and 16 weeks
Difference in total cholesterol levels between 8 and 16 weeks.
Total cholesterol changes according to time of intake of antihypertensive drugs
Measured: 8 and 16 weeks
Difference in p-creatinine levels between 8 and 16 weeks.
P-creatinine changes according to time of intake of antihypertensive drugs
Measured: 8 and 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2022
- Study start25 Jun 2022
- Primary completion1 Jun 2025 (estimated)
- Study completion1 Jun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for HypertensionStudies of the same condition, open and under way.
- More trials run by Vastra Gotaland RegionThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Participants are randomized in the initial phase to take their ordinary anti-hypertensive medication in the morning or at bedtime for 8 weeks. Then the participants are switching to the alternative intervention during 8 weeks in the second phase of the study.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vastra Gotaland Region
- Sponsor type
- Other government
- Collaborators
- Swedish Heart Lung Foundation
- Responsible party
- Sponsor
- Investigators
- Karin Manhem, Prof, MD, Principal investigator, Sahlgrenska University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05322967
- Sponsor's protocol ID
- VGFOUREG-939529
- Status last verified
- Apr 2024
- First submitted
- 4 Apr 2022
- Last updated
- 20 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hermida RC, Crespo JJ, Dominguez-Sardina M, Otero A, Moya A, Rios MT, Sineiro E, Castineira MC, Callejas PA, Pousa L, Salgado JL, Duran C, Sanchez JJ, Fernandez JR, Mojon A, Ayala DE; Hygia Project Investigators. Bedtime hypertension treatment improves cardiovascular risk reduction: the Hygia Chronotherapy Trial. Eur Heart J. 2020 Dec 21;41(48):4565-4576. doi: 10.1093/eurheartj/ehz754.
PubMed 31641769Hermida RC. Sleep-time ambulatory blood pressure as a prognostic marker of vascular and other risks and therapeutic target for prevention by hypertension chronotherapy: Rationale and design of the Hygia Project. Chronobiol Int. 2016;33(7):906-36. doi: 10.1080/07420528.2016.1181078. Epub 2016 May 24.
PubMed 27221952Fujiwara T, Hoshide S, Yano Y, Kanegae H, Kario K. Comparison of morning vs bedtime administration of the combination of valsartan/amlodipine on nocturnal brachial and central blood pressure in patients with hypertension. J Clin Hypertens (Greenwich). 2017 Dec;19(12):1319-1326. doi: 10.1111/jch.13128. Epub 2017 Nov 5.
PubMed 29106031Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991 Dec;14(6):540-5. doi: 10.1093/sleep/14.6.540.
PubMed 1798888Bilo G, Grillo A, Guida V, Parati G. Morning blood pressure surge: pathophysiology, clinical relevance and therapeutic aspects. Integr Blood Press Control. 2018 May 24;11:47-56. doi: 10.2147/IBPC.S130277. eCollection 2018.
PubMed 29872338Bowles NP, Thosar SS, Herzig MX, Shea SA. Chronotherapy for Hypertension. Curr Hypertens Rep. 2018 Sep 28;20(11):97. doi: 10.1007/s11906-018-0897-4.
PubMed 30267334Callaway E, Ledford H. Medicine Nobel awarded for work on circadian clocks. Nature. 2017 Oct 2;550(7674):18. doi: 10.1038/nature.2017.22736. No abstract available.
PubMed 289806622018 Practice Guidelines for the management of arterial hypertension of the European Society of Hypertension and the European Society of Cardiology: ESH/ESC Task Force for the Management of Arterial Hypertension: Erratum. J Hypertens. 2019 Feb;37(2):456. doi: 10.1097/HJH.0000000000002026. No abstract available.
PubMed 30640882
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Chronotherapy in Hypertension - a Study of Blood Pressure Levels Following Intake of Antihypertensive Medication in the Morning or at Bedtime
- ClinicalTrials.gov ID
- NCT05322967
- Acronym / sponsor ID
- VGFOUREG-939529
- Conditions
- Hypertension, Drug Therapy, Primary Health Care
- Keywords
- Cross-over study
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Vastra Gotaland RegionOther government
- Collaborators
- Swedish Heart Lung Foundation
- Study start
- 25 Jun 2022 (actual)
- Primary completion
- 1 Jun 2025 (estimated)
- Study completion
- 1 Jun 2025 (estimated)
- First posted
- 12 Apr 2022 (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.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Participants are randomized in the initial phase to take their ordinary anti-hypertensive medication in the morning or at bedtime for 8 weeks. Then the participants are switching to the alternative intervention during 8 weeks in the second phase of the study.
| Arm | Type | Receives |
|---|---|---|
| Morning intake | Active comparator | Other: Time of ordinary antihypertensive medication intakeIntake of antihypertensive medication in the morning |
| Bedtime intake | Active comparator | Other: Time of ordinary antihypertensive medication intakeIntake of antihypertensive medication at bedtime |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Diagnosis of hypertension
- Stable antihypertensive treatment at least 8 weeks prior to inclusion
- One to four antihypertensive drugs
Key exclusion criteria (8 listed)
- Atrial fibrillation/flutter
- Diabetes
- Previous stroke or TIA
- Heart failure
- Ischemic heart disease
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 |
|---|---|---|
| Time of ordinary antihypertensive medication intakeTime of ordinary antihypertensive medication intake | Other | Bedtime intake, Morning intake |
Primary outcome
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.
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 secondary outcomes
Daytime blood pressure changes between 8 and 16 weeks.
Time frame: 8 and 16 weeks
Nighttime blood pressure changes between 8 and 16 weeks.
Time frame: 8 and 16 weeks
Office blood pressure changes between 8 and 16 weeks.
Time frame: 8 and 16 weeks
Difference in morning surge of blood pressure between 8 and 16 weeks.
Time frame: 8 and 16 weeks
Difference in LDL cholesterol levels between 8 and 16 weeks.
Time frame: 8 and 16 weeks
Difference in HDL cholesterol levels between 8 and 16 weeks.
Time frame: 8 and 16 weeks
Difference in total cholesterol levels between 8 and 16 weeks.
Time frame: 8 and 16 weeks
Difference in p-creatinine levels between 8 and 16 weeks.
Time frame: 8 and 16 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2024.
- Background: PubMed 31641769Hermida RC, Crespo JJ, Dominguez-Sardina M, Otero A, Moya A, Rios MT, Sineiro E, Castineira MC, Callejas PA, Pousa L, Salgado JL, Duran C, Sanchez JJ, Fernandez JR, Mojon A, Ayala DE; Hygia Project Investigators. Bedtime hypertension treatment improves cardiovascular risk reduction: the Hygia Chronotherapy Trial. Eur Heart J. 2020 Dec 21;41(48):4565-4576. doi: 10.1093/eurheartj/ehz754.
- Background: PubMed 27221952Hermida RC. Sleep-time ambulatory blood pressure as a prognostic marker of vascular and other risks and therapeutic target for prevention by hypertension chronotherapy: Rationale and design of the Hygia Project. Chronobiol Int. 2016;33(7):906-36. doi: 10.1080/07420528.2016.1181078. Epub 2016 May 24.
- Background: PubMed 29106031Fujiwara T, Hoshide S, Yano Y, Kanegae H, Kario K. Comparison of morning vs bedtime administration of the combination of valsartan/amlodipine on nocturnal brachial and central blood pressure in patients with hypertension. J Clin Hypertens (Greenwich). 2017 Dec;19(12):1319-1326. doi: 10.1111/jch.13128. Epub 2017 Nov 5.
- Background: PubMed 1798888Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991 Dec;14(6):540-5. doi: 10.1093/sleep/14.6.540.
- Background: PubMed 29872338Bilo G, Grillo A, Guida V, Parati G. Morning blood pressure surge: pathophysiology, clinical relevance and therapeutic aspects. Integr Blood Press Control. 2018 May 24;11:47-56. doi: 10.2147/IBPC.S130277. eCollection 2018.
- Background: PubMed 30267334Bowles NP, Thosar SS, Herzig MX, Shea SA. Chronotherapy for Hypertension. Curr Hypertens Rep. 2018 Sep 28;20(11):97. doi: 10.1007/s11906-018-0897-4.
- Background: PubMed 28980662Callaway E, Ledford H. Medicine Nobel awarded for work on circadian clocks. Nature. 2017 Oct 2;550(7674):18. doi: 10.1038/nature.2017.22736. No abstract available.
- Background: PubMed 306408822018 Practice Guidelines for the management of arterial hypertension of the European Society of Hypertension and the European Society of Cardiology: ESH/ESC Task Force for the Management of Arterial Hypertension: Erratum. J Hypertens. 2019 Feb;37(2):456. doi: 10.1097/HJH.0000000000002026. No abstract available.
- 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.
Karin Manhem, Prof, MD principal investigator
Sahlgrenska University Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Time of ordinary antihypertensive medication intake in people with Hypertension and Drug Therapy, run by Vastra Gotaland Region at 3 sites in Sweden.
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 3 inclusion and 8 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: status not confirmed, as of the sponsor's last update on 20 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Sweden. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Kristina B Boström, Prof, MD (0702409091, kristina.a.bengtsson@vgregion.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
24 hours blood pressure changes between 8 and 16 weeks. (time frame: 8 and 16 weeks). The study lists 2 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 NCT05322967, which also lists 8 linked publications.
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 20 Aug 2024.