Effect of Physical Exercise in Alzheimer Patients

NCT01681602 | Completed Phase 3 DMC

• 1 other identifier: H-3-2011-128
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

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.

Conditions

Alzheimer Disease

Keywords

Alzheimer Disease; Exercise; Cognition; Quality of life; Cardiovascular fitness; Behavioural or psychological symptoms; Physical fitness

Outcome Measures

Primary Outcomes (1)

• Symbol Digit Modalities Test

  Change in score from baseline to 16 weeks

Secondary Outcomes (9)

• NPI (psychological symptoms.)

  Change in score from baseline to 16 weeks

• Astrand submaximal bicycle test for estimating VO2 max

  Change in score from baseline to 16 weeks

• Euro-qol-5D-5L (health related quality of life)

  Change in score from baseline to 16 weeks

• Alzheimer's disease Assessment Scale - Cognitive section (ADAS-cog).

  Change in score from baseline to 16 weeks

• Changes in physical fitness

  Change in score from baseline to 16 weeks

Study Arms (2)

Intervention group

ACTIVE COMPARATOR

16 weeks of aerobic exercise

Other: Aerobic exercise

Control group

NO INTERVENTION

Usual care.

Interventions

Aerobic exercise OTHER

Physical exercise in the intervention group will be delivered as an individually tailored program consisting of 4 weeks of adaptation exercise followed by 12 weeks of continuously supervised moderate aerobic exercise 1 hour three times a week. The participants can choose from treadmill, stationary bike and crosstrainer.

Also known as: Endurance training

Intervention group

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead

Study Sites (1)

Danish Dementia Research Centre, Department of Neurology, Rigshospitalet.

Copenhagen, Copenhagen Ø, 2100, Denmark

Location

Related Publications (6)

• Delgado-Peraza F, Nogueras-Ortiz C, Simonsen AH, Knight DD, Yao PJ, Goetzl EJ, Jensen CS, Hogh P, Gottrup H, Vestergaard K, Hasselbalch SG, Kapogiannis D. Neuron-derived extracellular vesicles in blood reveal effects of exercise in Alzheimer's disease. Alzheimers Res Ther. 2023 Sep 20;15(1):156. doi: 10.1186/s13195-023-01303-9.

  PMID: 37730689 DERIVED

• Frederiksen KS, Jensen CS, Hogh P, Gergelyffy R, Waldemar G, Andersen BB, Gottrup H, Vestergaard K, Wermuth L, Sondergaard HB, Sellebjerg F, Hasselbalch SG, Simonsen AH. Aerobic exercise does not affect serum neurofilament light in patients with mild Alzheimer's disease. Front Neurosci. 2023 Jan 24;17:1108191. doi: 10.3389/fnins.2023.1108191. eCollection 2023.

  PMID: 36761410 DERIVED

• 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.

  PMID: 35249488 DERIVED

• 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.

  PMID: 33246408 DERIVED

• 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.

  PMID: 30319397 DERIVED

• 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.

  PMID: 28615271 DERIVED

MeSH Terms

Conditions

Alzheimer Disease; Motor Activity

Interventions

Exercise; Endurance Training

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Behavior

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Physical Therapy Modalities; Physical Conditioning, Human

Study Officials

• Steen G Hasselbalch, Professor

  Memory Disorders Research Group, Department of Neurology, Copenhagen University Hospital, Rigshospitalet

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: April 30, 2012
• First Posted: September 10, 2012
• Study Start: January 1, 2012
• Primary Completion: January 1, 2014
• Study Completion: June 1, 2014
• Last Updated: December 2, 2014

Record last verified: 2014-11

Locations

DK (1)