Clinical Trials

AMBAR (Alzheimer's Management By Albumin Replacement)

Trial of therapeutic plasma exchange with albumin replacement in mild-moderate Alzheimer's. Showed slowed cognitive decline in moderate-disease subgroup — a proof-of-concept for plasma-based rejuvenation strategies.

ASPREE (Aspirin in Reducing Events in the Elderly)

Largest primary-prevention aspirin trial in healthy older adults. Showed no cardiovascular benefit, increased bleeding, and (unexpectedly) a small increase in all-cause and cancer mortality. Reshaped aspirin guidelines.

CALERIE — Caloric Restriction in Non-Obese Humans

The first long-term RCT of caloric restriction in non-obese adults, showing cardiometabolic improvements, modest reduction in epigenetic-age acceleration, and acceptable quality of life over 2 years.

CANTOS — Canakinumab Anti-Inflammatory Trial

The first RCT to show that targeting inflammation (IL-1β) — without changing lipids — reduces cardiovascular events and (unexpectedly) lung cancer incidence.

DAPA-HF & EMPEROR-Reduced

Two landmark trials proving SGLT2 inhibitors reduce death and heart-failure hospitalisation in HFrEF, including non-diabetic patients. Reshaped guideline-directed medical therapy.

Diabetes Prevention Program (DPP)

Landmark US RCT showing that intensive lifestyle intervention prevented incident type-2 diabetes by 58% in pre-diabetic adults — more than metformin (31%) — over 3 years.

DO-HEALTH

Large European RCT in healthy older adults testing vitamin D, omega-3, and a home exercise programme on a composite of healthspan endpoints.

EAST-AFNET 4 (Early Rhythm Control in AFib)

Showed that early rhythm-control therapy (antiarrhythmic drugs or ablation) reduces cardiovascular events vs. rate-control alone in newly diagnosed AFib — overturning decades of equivalence dogma.

EMPA-REG OUTCOME — Empagliflozin in High-Risk T2D

The trial that turned SGLT2 inhibitors from glucose-lowering drugs into cardiovascular- and kidney-protective agents.

FINGER — Multidomain Intervention to Prevent Cognitive Decline

The first RCT to show that a multidomain lifestyle intervention slows cognitive decline in at-risk older adults.

FLOW (Semaglutide in Diabetic Kidney Disease)

Confirmed semaglutide reduces major kidney and cardiovascular events in type-2 diabetes with chronic kidney disease — adding kidney benefit to the GLP-1 evidence base.

FOURIER — Evolocumab (PCSK9 Inhibitor) in ASCVD

Showed that PCSK9 inhibition added to statin therapy further reduces cardiovascular events in established ASCVD by aggressively lowering LDL.

JUPITER — Rosuvastatin in Healthy Adults with Elevated hsCRP

Tested rosuvastatin in adults with normal LDL but elevated hsCRP; showed major cardiovascular event reduction, validating both statins and inflammation as targets.

LookAHEAD (Lifestyle Intervention in T2D)

Large RCT of intensive lifestyle intervention in obese T2D adults. Stopped early for futility on cardiovascular endpoint despite substantial weight loss — a cautionary tale about lifestyle as cure for established disease.

NIA Interventions Testing Program (ITP)

NIA-funded multi-site programme that tests candidate interventions for lifespan extension in genetically heterogeneous mice using a rigorous, pre-registered, replicated design.

PEARL — Participatory Evaluation of Aging with Rapamycin

One of the first decentralised RCTs of low-dose rapamycin in healthy older adults, measuring functional, body-composition, and quality-of-life endpoints.

PREDIMED (Mediterranean Diet)

Spanish primary-prevention RCT showing Mediterranean diet supplemented with extra-virgin olive oil or mixed nuts reduced major cardiovascular events by ~30% over 5 years in high-risk adults.

REDUCE-IT — Icosapent Ethyl in High-Triglyceride ASCVD Patients

Showed that high-dose pure EPA (icosapent ethyl 4 g/day) reduces major cardiovascular events in statin-treated patients with elevated triglycerides.

SELECT — Semaglutide in Obesity Without Diabetes

Established that semaglutide reduces major adverse cardiovascular events by 20% in obese adults without diabetes — a paradigm-shifting cardiovascular outcomes result.

SPRINT — Intensive vs Standard Blood-Pressure Control

Showed that targeting systolic BP <120 vs <140 mmHg in high-risk older adults reduced cardiovascular events by 25% and all-cause mortality by 27%.

SPRINT-MIND (Intensive BP & Cognition)

Sub-study of SPRINT showing intensive blood-pressure control reduced incident mild cognitive impairment, though not dementia itself, over ~5 years.

SURMOUNT (Tirzepatide for Obesity)

Phase 3 programme establishing tirzepatide (dual GIP/GLP-1 agonist) as the most potent currently approved obesity drug, with weight-loss outcomes approaching bariatric surgery.

TAME — Targeting Aging with Metformin

Planned multicentre RCT proposing to use metformin in non-diabetic older adults to delay the onset of multiple age-related diseases simultaneously.

VITAL — Vitamin D and Omega-3 in Primary Prevention

Large primary-prevention trial that found no benefit of vitamin D or omega-3 for cardiovascular or cancer endpoints, with some signal for autoimmune disease prevention.