Shantou Amsterdam study on blood pressure reduction and dementia prevention

ISRCTN	ISRCTN13752095
DOI	https://doi.org/10.1186/ISRCTN13752095
Sponsors	First Affiliated Hospital of Shantou University Medical College, Shantou University Medical College
Funders	Pro Senectute, Alzheimer Nederland, Shantou University Medical College, First Affiliated Hospital of Shantou University Medical College

Submission date: 17/07/2026
Registration date: 17/07/2026
Last edited: 17/07/2026

Recruitment status: Not yet recruiting
Overall study status: Ongoing
Condition category: Nervous System Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
Hypertension in midlife is a well-established risk factor for dementia in later life, and blood pressure lowering using antihypertensive treatment may reduce dementia risk. Observational studies suggest that specific classes of antihypertensive medication (AHM), particularly angiotensin receptor blockers (ARBs), may confer additional neuroprotective effects beyond blood pressure lowering. Current (inter)national guidelines consider all AHM classes to be equally effective for blood pressure management and cardiovascular disease prevention, except in individuals with specific comorbidities. The aim of this study is to determine whether long-term use of an AHM strategy based on ARBs, compared to the ones based on ACE inhibitors (ACEi) reduces the incidence of cognitive decline and dementia.

Who can participate?
Individuals aged 65–80 with untreated hypertension and without dementia.

What does the study involve?
Participants are randomly assigned to one of the two treatment groups (ARBs or ACEi) and undergo follow-up assessments of their cognitive functioning at one, three, and five years. Additionally, incident cardiovascular disease (including myocardial infarction and stroke), cardiovascular and all-cause death, and daily functioning are measured.

What are the possible benefits and risks of participating?
Treatment in both groups follow existing clinical guidelines for treating hypertension. The risks associated with participation are comparable to those of standard care and primarily involve the known side effects of high blood pressure medication.

Where is the study run from?
Amsterdam University Medical Center, Netherlands. The study is conducted across 34 primary care community health centres in the Shantou region, China

When is the study starting and how long is it expected to run for?
August 2026 to August 2033. Intervention and follow-up last five years.

Who is funding the study?
1. First Affiliated Hospital of Shantou University Medical College
2. Shantou University Medical College
3. Pro Senectute
4. Alzheimer Nederland

Who is the main contact?
Tzu Han Chang, t.h.chang@amsterdamumc.nl

Contact information

Prof Edo Richard
Principal investigator, Scientific, Public

Amsterdam UMC
Meibergdreef 9
Amsterdam
1105 AZ
Netherlands

ORCID ID	0000-0002-7250-3390
Phone	+31 (0)20 566 9111
Email	Edo.richard@radboudumc.nl

Prof Eric Moll van Charante
Principal investigator, Scientific, Public

Amsterdam UMC
Meibergdreef 9
Amsterdam
1105 AZ
Netherlands

ORCID ID	0000-0002-1489-5218
Phone	+31 (0)20 566 9111
Email	E.p.mollvancharante@amsterdamumc.nl

Prof Wei Wang
Principal investigator, Scientific, Public

Shantou University Medical College
No. 22 Xinling Road
Jinping District
Shantou
515041
China

ORCID ID	0000-0002-1430-1360
Phone	+86 754 8825 8290
Email	Wei.wang@ecu.edu.au

Prof Xuerui Tan
Principal investigator, Scientific

First Affiliated Hospital of Shantou University Medical College
No. 57 Changping Road
Jinping District
Shantou
515041
China

ORCID ID	0000-0001-5637-1749
Phone	+86 754 8825 8290
Email	Doctortxr@126.com

Prof Yequn Chen
Principal investigator, Scientific

First Affiliated Hospital of Shantou University Medical College
No. 57 Changping Road
Jinping District
Shantou
515041
China

ORCID ID	0009-0008-6425-3847
Phone	+86 754 8825 8290
Email	Gdcycyq@163.com

Study information

Primary study design	Interventional
Allocation	Randomized controlled trial
Masking	Open (masking not used)
Control	Active
Assignment	Parallel
Purpose	Prevention
Scientific title	Shantou-Amsterdam study on blood pressure Reduction and dementia Prevention (SHARP)
Study acronym	SHARP
Study objectives	To determine whether long-term use of an antihypertensive treatment strategy based on angiotensin receptor blockers (ARBs), compared to one based on ACE inhibitors (ACEi), reduces the incidence of cognitive decline and dementia.
Ethics approval(s)	Approved 08/05/2026, The Ethics Committee of First Affiliated Hospital of Shantou University Medical College (No. 57 Changping Road, Jinping District, Shantou, 515041, China; +86 754-88905647; sdfyllwyh@163.com), ref: B-2026-094
Health condition(s) or problem(s) studied	Dementia, cognitive decline, hypertension
Intervention	The study is a two-arm, randomized controlled clinical trial using a prospective, open-label, blinded endpoint (PROBE) design. The study is conducted in China. Participants with newly diagnosed hypertension receive oral antihypertensive medication (AHM) in accordance with the national Chinese guidelines, which align with international recommendations for the management of primary hypertension. Randomization is performed centrally via the electronic CRF. Participants are randomized to four treatment groups (1:1:1:1), which differ in the sequence of second- and third-line therapy. For the primary analysis, these groups are combined into two treatment arms (ARB-based vs. ACEi-based). - Groups 1–2 (Intervention): Protocolized, stepped antihypertensive treatment initiated with an ARB, with dihydropyridine calcium channel blocker (diCCB) and thiazide allocated as second- and third-line therapy in alternate sequences. - Groups 3–4 (Comparator): Protocolized, stepped antihypertensive treatment initiated with an ACEi, with diCCB and thiazide allocated as second- and third-line therapy in alternate sequences. Since hyperuricemia (serum uric acid level >420 μmol/L or >7 mg/dL) is a contraindication for thiazides, individuals with these conditions follow an adapted treatment scheme. The same scheme is also provided to those with hypokalemia. For all groups, a beta-blocker may be added as fourth-line therapy if needed. Dosage modifications follow a predefined stepwise protocol to achieve blood pressure control (Systolic Blood Pressure (SBP) ≤ 140 mmHg and diastolic blood pressure (DBP) ≤ 90 mmHg). At treatment initiation and after each medication adjustment (dose change or addition), a 4-week follow-up is scheduled to assess blood pressure. Laboratory tests are performed as needed. If the blood pressure is adequately controlled and no safety concerns are identified, treatment is continued and reassessed after 6 months. If blood pressure remains controlled at that point, the same treatment is continued and reviewed at the 1-year assessment, after which monitoring continues at regular intervals for the remainder of the five-year intervention period. Intervention and follow-up last five years.
Intervention type	Drug
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Angiotensin receptor blockers, ACE inhibitors, Dihydropyridine calcium channel blocker, Thiazide, Beta-blockers
Primary outcome measure(s)	Clinical diagnosis of all-cause dementia at any time during the study and/or clinically meaningful cognitive decline measured using >3-point decrease on the Mini Mental State Examination (MMSE) versus baseline at baseline, 1, 3 and 5 and five years
Key secondary outcome measure(s)	All-cause dementia measured using data collection on the clinical diagnosis made at any time during the study Cognitive decline measured using >3-point decrease on the MMSE versus baseline at baseline, 1, 3 and 5 and five years Incident cardiovascular events (myocardial infarction and stroke) measured using self-report at study assessments via electronic CRF, and using primary care records, hospital records, and/or death registry at any time during the study Cardiovascular and all-cause death measured using primary care records, hospital records, and/or death registry at any time during the study Changes in daily functioning from baseline measured using the Lawton Instrumental activity of daily living scale at baseline and daily at any time during the study
Completion date	01/08/2033

Eligibility

Participant type(s)
Age group	Senior
Lower age limit	65 Years
Upper age limit	80 Years
Sex	All
Target sample size at registration	9000
Key inclusion criteria	1. Individuals aged 65–80 years 2. Not currently on AHM 3. Willing to receive regular (ATC-listed) antihypertensive treatment 4. Current mean SBP ≥140 and/or DBP ≥90 mmHg 5. Who are either: 5.1. Newly diagnosed with primary hypertension 5.2. Previously diagnosed but never treated; or 5.3. Previously treated but stopped AHM >3 years before baseline
Key exclusion criteria	1. Current use of AHM 2. Dementia or relevant cognitive decline (defined as MMSE < 24 points; or < 21 points for ISCED level 1) 3. Contra-indications to use of an ARB or an ACEi
Date of first enrolment	01/08/2026
Date of final enrolment	01/08/2028

Locations

Countries of recruitment

China

Study participating centre

First Affiliated Hospital of Shantou University Medical College

No. 57 Changping Road
Jinping District
Shantou
515041
China

Results and Publications

Individual participant data (IPD) Intention to share	No

Editorial Notes

17/07/2026: Study’s existence confirmed by the Ethics Committee of First Affiliated Hospital of Shantou University Medical College, China.