Clinical trial NCT01681602: Effect of Physical Exercise in Alzheimer Patients
Official title: Preserving Quality of Life, Physical Health and Functional Ability in Alzheimer's Disease: The Effect of Physical Exercise
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Alzheimer Disease
Keywords: Alzheimer Disease
Exercise
Cognition
Quality of life
Cardiovascular fitness
Behavioural or psychological symptoms
Physical fitness
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2012-09-10
Enrollment: 200
Sex: ALL
Minimum age (years): 50
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Background: Current treatment for Alzheimer's disease (AD) is symptomatic and can only temporarily slow down progression.

Exercise has the potential to improve cognition, psychological symptoms, physical performance and quality of life, but evidence is scarce. Previous trials are short, often underpowered and involving home based light exercise programs. Most have included nursing homes residents with severe or undefined dementia. The aim of the ADEX trial is to establish whether exercise is effective in improving cognition, physical performance and quality of life as well as reducing the prevalence of psychological symptoms among AD patients.

Methods: The ADEX Trial is a multicentre, single-blind, randomized clinical trial. Based on power calculations the investigators plan to recruit 192 home-dwelling patients aged 50-90 years with mild to moderate AD. The participants will be randomly allocated into two groups: An intervention group attending 16 weeks of continuously supervised moderate aerobic exercise 1 hour three times a week and a control group only receiving usual care. The hypothesis is that aerobic exercise will improve physical function, the cognitive and daily functioning and quality of life in people with mild to moderate AS.

Blood sampling will be performed in all subjects to examine effects on biomarkers. A subgroup of the patients will also undergo MRI, PiB-PET and lumbar puncture to investigate structural changes and β-amyloid accumulation.

Further, a health-economic analysis will be performed.

Recruitment was started in January 2012. Last study visits are planned to be performed in January 2014 and results will be available in 2014. This RCT will contribute to evidence regarding the potential effects of a systematic program of physical exercise for patients with Alzheimer's disease.

Detailed description: see protocol article

Eligibility criteria: Inclusion Criteria:

* Inclusion criteria are (table 1)
* Age between 50 and 90 years
* A score of 20 or more on the Mini Mental State Examination (MMSE)
* Imaging (CT or MR of cerebrum) consistent with AD
* Have a caregiver with regular contact to the participant (more than once a month) who is also willing to participate in the study
* In general good health allowing the participant to participate in physical exercise.
* At least 7 years of schooling and Danish speaking
* Visual acuity and hearing must permit neuropsychological testing.
* If the patient is receiving anti-dementia medication or mood stabilizing medication, these must have been given in stable doses for at least 3 months.

Exclusion Criteria:

* Participation in aerobic exercise (moderate to hard intensity) more than 2 times a week on a regular basis.
* Any musculoskeletal or joint impairment that could interfere with completion of the study (significant joint problems, back pain or pain in arms and legs that provide problems with mobility in daily activities)
* Male participants with a combination of two or more of the following risk factors even if asymptomatic: smokers, hypertension and hypercholesterolemia
* Major neurologic (other than AD), cardiac or other medical diseases that constitutes a contraindication to physical activity. Stent operation or previous myocardial infarction is not an exclusion criteria if the participant has had a recent (within 3 months) normal exercise tests .
* Severe cerebro vascular disease judged from the CT or MR scans and remarkable hypertension defined as Systolic blood pressure \>180 and diastolic \>100
* Severe psychiatric disease, as well as alcohol or drug abuse within the last 2 years

Primary outcomes:
measure: Symbol Digit Modalities Test
timeFrame: Change in score from baseline to 16 weeks
Secondary outcomes:
measure: NPI (psychological symptoms.)
timeFrame: Change in score from baseline to 16 weeks
measure: Astrand submaximal bicycle test for estimating VO2 max
timeFrame: Change in score from baseline to 16 weeks
measure: Euro-qol-5D-5L (health related quality of life)
timeFrame: Change in score from baseline to 16 weeks
measure: Alzheimer's disease Assessment Scale - Cognitive section (ADAS-cog).
timeFrame: Change in score from baseline to 16 weeks
measure: Changes in physical fitness
timeFrame: Change in score from baseline to 16 weeks
measure: Self-efficacy scale
timeFrame: Change in score from baseline to 16 weeks
measure: Verbal fluency
timeFrame: Change in score from baseline to 16 weeks
measure: Stroop
timeFrame: Change in score from baseline to 16 weeks
measure: MMSE (Mini Mental State Examination)
timeFrame: Change in score from baseline to 16 weeks
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Danish Dementia Research Centre, Department of Neurology, Rigshospitalet.
state: Copenhagen Ø
Study officials:
affiliation: Memory Disorders Research Group, Department of Neurology, Copenhagen University Hospital, Rigshospitalet
name: Steen G Hasselbalch, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Musaeus CS, Johansen LB, Hasselbalch S, Beyer N, Hogh P, Siebner HR, Frederiksen KS. Sixteen Weeks of Aerobic Exercise does not Alter Resting-state Connectivity of the Precuneus in Patients with Alzheimer's Disease. Curr Alzheimer Res. 2022;19(2):171-177. doi: 10.2174/1567205019666220304091241.
citation: Clemmensen FK, Hoffmann K, Siersma V, Sobol N, Beyer N, Andersen BB, Vogel A, Lolk A, Gottrup H, Hogh P, Waldemar G, Hasselbalch SG, Frederiksen KS. The role of physical and cognitive function in performance of activities of daily living in patients with mild-to-moderate Alzheimer's disease - a cross-sectional study. BMC Geriatr. 2020 Nov 27;20(1):513. doi: 10.1186/s12877-020-01926-9.
citation: Frederiksen KS, Larsen CT, Hasselbalch SG, Christensen AN, Hogh P, Wermuth L, Andersen BB, Siebner HR, Garde E. A 16-Week Aerobic Exercise Intervention Does Not Affect Hippocampal Volume and Cortical Thickness in Mild to Moderate Alzheimer's Disease. Front Aging Neurosci. 2018 Sep 25;10:293. doi: 10.3389/fnagi.2018.00293. eCollection 2018.
citation: Sopina E, Sorensen J, Beyer N, Hasselbalch SG, Waldemar G. Cost-effectiveness of a randomised trial of physical activity in Alzheimer's disease: a secondary analysis exploring patient and proxy-reported health-related quality of life measures in Denmark. BMJ Open. 2017 Jun 14;7(6):e015217. doi: 10.1136/bmjopen-2016-015217.