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

NCT ID: NCT05322967

Last Updated: 2024-08-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-25
• Study Completion Date: 2025-06-01

Brief 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. 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.

Conditions

Hypertension; Drug Therapy; Primary Health Care

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Morning intake

Intake of antihypertensive medication in the morning

Group Type: ACTIVE_COMPARATOR

Time of ordinary antihypertensive medication intake

Intervention Type: OTHER

Time of ordinary antihypertensive medication intake

Bedtime intake

Intake of antihypertensive medication at bedtime

Group Type: ACTIVE_COMPARATOR

Time of ordinary antihypertensive medication intake

Intervention Type: OTHER

Time of ordinary antihypertensive medication intake

Interventions

Time of ordinary antihypertensive medication intake

Time of ordinary antihypertensive medication intake

Intervention Type: OTHER

Eligibility Criteria

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)

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Swedish Heart Lung Foundation

OTHER

Sponsor Role: collaborator

Vastra Gotaland Region

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Karin Manhem, Prof, MD

Role: PRINCIPAL_INVESTIGATOR

Sahlgrenska University Hospital

Locations

Sahlgrenska University Hospital, Mölndal

Gothenburg, , Sweden

Site Status: RECRUITING

Närhälsan Billingen Primary Health Care Centre

Skövde, , Sweden

Site Status: RECRUITING

Närhälsan Norrmalm Primary Health Care Centre

Skövde, , Sweden

Site Status: NOT_YET_RECRUITING

Countries

Sweden

Central Contacts

Kristina B Boström, Prof, MD

Role: CONTACT

kristina.a.bengtsson@vgregion.se

0702409091

Georgios Mourtzinis, PhD, MD

Role: CONTACT

georgios.mourtzinis@vgregion.se

0735522153

Facility Contacts

Johan-Emil Bager, PhD, MD

Role: primary

johan-emil.bager@vgregion.se

+46739728299

Kristina Bengtsson Boström

Role: primary

kristina.a.bengtsson@vgregion.se

+46702409091

Tobias Andersson

Role: primary

tobias.e.andersson@vgregion.se

+46707 143437

References

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.

Reference Type: BACKGROUND

PMID: 31641769 (View on PubMed)

Hermida 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.

Reference Type: BACKGROUND

PMID: 27221952 (View on PubMed)

Fujiwara 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.

Reference Type: BACKGROUND

PMID: 29106031 (View on PubMed)

Johns 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.

Reference Type: BACKGROUND

PMID: 1798888 (View on PubMed)

Bilo 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.

Reference Type: BACKGROUND

PMID: 29872338 (View on PubMed)

Bowles 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.

Reference Type: BACKGROUND

PMID: 30267334 (View on PubMed)

Callaway 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.

Reference Type: BACKGROUND

PMID: 28980662 (View on PubMed)

2018 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.

Reference Type: BACKGROUND

PMID: 30640882 (View on PubMed)

Other Identifiers

VGFOUREG-939529

Identifier Type: -

Identifier Source: org_study_id