Multimodal Preventive Trial for Alzheimer's Disease (MIND-ADmini)

• ClinicalTrials.gov Identifier: NCT03249688
• Recruitment Status: Completed
• First Posted: August 15, 2017
• Last Update Posted: September 23, 2021
• Sponsor: Karolinska Institutet
• Collaborators: University of Eastern Finland; Universität des Saarlandes; University Hospital, Toulouse
• Information provided by (Responsible Party): Miia Kivipelto, Karolinska Institutet

Study Description

Brief Summary:

The main aim of the MIND-ADmini pilot trial is to evaluate the feasibility of a multimodal lifestyle intervention among patients with prodromal AD.

Condition or disease	Intervention/treatment	Phase
Alzheimer Disease; Prodromal	Other: Regular health advice; Behavioral: Multidomain lifestyle; Dietary Supplement: Medical food	Not Applicable

Detailed Description:

Given the multifactorial etiology of Alzheimer's disease (AD), multimodal interventions targeting several risk factors and disease mechanisms simultaneously are most likely to be effective for preventing dementia. Multimodal lifestyle interventions have so far been tested in at-risk older adults from the general population, but not in patients with prodromal AD.

The main aim of the MIND-ADmini pilot trial is to evaluate the feasibility of a multimodal lifestyle intervention among individuals with prodromal AD.

This 6-month pilot trial is planned to include 150 participants randomized into 3 arms:

1. Control (regular health advice)
2. Multidomain lifestyle intervention (nutritional guidance, exercise, cognitive training and monitoring and management of vascular and metabolic risk factors)
3. Multidomain lifestyle intervention + medical food. The multidomain lifestyle intervention is adapted from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER, NCT01041989). The medical food product includes the specific multi-nutrient combination Fortasyn Connect (containing the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), uridine monophosphate, choline, vitamins B12, B6, C, E, and folic acid, phospholipids, and selenium). The rationale for combining a multidomain lifestyle intervention with medical food is evidence indicating synergistic effects between different intervention components (e.g. omega-3 fatty acids and physical activity). Nutrient deficiencies have been described in AD, and medical food may be needed in addition to dietary guidance for optimal effect. The use of Fortasyn Connect alone in prodromal AD has been investigated in another clinical trial (www.lipididiet.eu), and thus this arm is not included in MIND-ADmini.

The 6-month MIND-ADmini pilot trial will be conducted in Sweden, Finland, Germany and France. An additional 6-month optional extension of the pilot trial will also be considered.

Primary outcome is feasibility of the multimodal intervention. Secondary outcomes include adherence to intervention components (intervention arms), and adherence to healthy lifestyle changes (all arms). Detailed cognitive assessments (Neuropsychological Test Battery, NTB) and functional assessments (Clinical Dementia Rating, CDR; and Alzheimer's Disease Cooperative Study-Activities of Daily Living, ADCS-ADL) will also be conducted at baseline and 6-month visit for the purpose of obtaining reliable estimates of change over time for power calculations for a future larger multimodal intervention trial (MIND-ADmaxi).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 93 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Multimodal Preventive Trial for Alzheimer's Disease (MIND-ADmini Pilot Trial)
• Actual Study Start Date: October 16, 2017
• Actual Primary Completion Date: December 23, 2019
• Actual Study Completion Date: December 18, 2020

Arms and Interventions

Arm	Intervention/treatment
Control; Regular health advice	Other: Regular health advice; Routine healthy lifestyle counseling
Experimental: Multidomain 1; Multidomain lifestyle	Behavioral: Multidomain lifestyle; Nutritional guidance, exercise, cognitive training, vascular risk monitoring
Experimental: Multidomain 2; Multidomain lifestyle + medical food	Behavioral: Multidomain lifestyle; Nutritional guidance, exercise, cognitive training, vascular risk monitoring; Dietary Supplement: Medical food; Medical food product (Fortasyn Connect)

Outcome Measures

Primary Outcome Measures :

1. Recruitment rate [ Time Frame: 6 months ]
   Recruitment rate of participants within a 6 months period
2. Overall adherence to the intervention [ Time Frame: 6 months ]
   Overall adherence to the intervention during 6 months
3. Retention rate [ Time Frame: 6 months ]
   Retention rate of participants during 6 months

Secondary Outcome Measures :

1. Adherence to intervention components [ Time Frame: 6 months ]
   Intervention arms only
2. Adherence to healthy lifestyle changes [ Time Frame: 6 months ]
   All arms

Other Outcome Measures:

1. Change in Body Mass Index [ Time Frame: 6 months ]
   Height (cm) and weight (kg) are used to calculate Body Mass Index
2. Change in Hip-waist ratio [ Time Frame: 6 months ]
   Hip and waist measurements (cm) are used for hip-waist ratio calculations
3. Change in blood pressure [ Time Frame: 6 months ]
   Including measurements of systolic blood pressure, diastolic blood pressure, and pulse pressure
4. Change in blood lipids [ Time Frame: 6 months ]
   Including measurements of serum total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides
5. Change in glucose metabolism markers [ Time Frame: 6 months ]
   Including measures of glucose, insulin, HbA1c
6. Change in inflammation [ Time Frame: 6 months ]
   CRP measures
7. Depressive symptoms [ Time Frame: 6 months ]
   Geriatric Depression Scale
8. Stress-related symptoms [ Time Frame: 6 months ]
   Perceived Stress Scale
9. Physical performance [ Time Frame: 6 months ]
   Timed 10-meter dual-task test & Short Physical Performance Battery (SPPB)
10. Health-related quality of life [ Time Frame: 6 months ]
    RAND36
11. Blood biomarkers [ Time Frame: 6 months ]
    e.g lipid metabolism, inflammation, vitamins (e.g D & B)
12. Self-reported adherence to each intervention component [ Time Frame: 6 months ]
    The following intervention components: nutrition, exercise, cognitive training, monitoring of vascular factors

Eligibility Criteria

• Ages Eligible for Study: 60 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion criteria:

A) Prodromal AD as defined as -1 SD on 2 out of 8 tests, at least 1 memory:

Memory FCSRT - delayed free recall* ≤ 8 FCSRT free recall - learning ≤ 22 WMS-R story delayed recall (%) ≤75% WMS-R delayed recall of figures (%) ≤ 75% *Free and Cued Selective reminding test

Non-memory TMT A ≥ 60 TMT B ≥ 150 Symbol Digit Substitution Test ≤ 35 (120 sec.) Category Fluency ≤ 16 (60 sec.)

• Evidence for underlying AD pathology within 2 year prior to screening by either:

  1. CSF beta amyloid 1-42/1-40x10 ratio<1 and/or elevated T-tau and/or elevated phospho-tau and/or low beta amyloid 42 based on local lab cut-offs OR
  2. MRI evidence for medial temporal lobe atrophy (MTA score 1 or higher) OR

  3. Abnormal FDG PET and/or PiB PET compatible with AD type change

     B) Potential for lifestyle improvement, defined according to a Lifestyle Index.

     Lifestyle index. Participants with a score of 3 or above are included in the study.

     The lifestyle index identifies individuals who do not already have very healthy lifestyles, and thus have a margin for improving their lifestyle based on the MIND-AD intervention. The score is calculated by adding 1 point for each of the following factors:

• Physical activity less than 2.5 hours a week (defined as physical activity intensive enough to lead to sweating and some breathlessness)
• Diet - less than 5 portions of fruits and vegetables per day
• Diet - less than 2 portions of fish per week
• Hypertension (diagnosed by physician or current antihypertensive treatment or
• SBP>140mmHg or DBP>90 mmHg)
• Diabetes (type 1 or 2 diagnosed by physician; or current diabetes medication; or recorded elevated fasting blood glucose or HbA1C as per local guidelines within the past 6 months)
• Ongoing symptoms of sleep problems, depressive symptoms or psychological stress symptoms for at least 1 month, judged by the clinician as having some impact on everyday life

C) Age 60-85 D) MMSE ≥ 24 E) Availability of a responsible study partner. F) Written informed consent from participant as well as study partner G) Putative prescription cognitive enhancers (e.g. ginkgo, cholinesterase inhibitors) and statins are not excluded but the dosage should be stable prior to randomization. Doses should be kept stable during the study if possible.

Exclusion criteria

• Dementia according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)
• Use of omega-3 preparations > 500mg EPA+DHA per day
• Alcohol or drug abuse
• A concomitant serious disease
• Major depressive disorder (DSM-IV)
• Regular intake of supplements for vitamin B6, B12, folic acid, vitamin C and/or E > 200% RDI, unless prescribed by physician
• Participation in any other clinical trial in the last 30 days
• Subjects with MRI (or CT) scan consistent with a diagnosis of stroke, intracranial bleeding, mass lesion or NPH. Those subjects with a MRI scan demonstrating minimal white matter changes (Fazekas scale for white matter lesions <=3) and up to 1-2 lacunar infarcts which are judged to be clinically insignificant are allowed
• Severe loss of vision or communicative ability
• Conditions preventing cooperation as judged by the study physician
• Concomitant participation in any intervention trial

Contacts and Locations

Locations

Sweden

Karolinska University Hospital

Huddinge, Sweden, 14186

Sponsors and Collaborators

Karolinska Institutet

University of Eastern Finland

Universität des Saarlandes

University Hospital, Toulouse

Investigators

• Principal Investigator: Miia Kivipelto, MD, PhD; Karolinska Institutet

More Information

Publications:

Ngandu T, Lehtisalo J, Solomon A, Levalahti E, Ahtiluoto S, Antikainen R, Backman L, Hanninen T, Jula A, Laatikainen T, Lindstrom J, Mangialasche F, Paajanen T, Pajala S, Peltonen M, Rauramaa R, Stigsdotter-Neely A, Strandberg T, Tuomilehto J, Soininen H, Kivipelto M. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet. 2015 Jun 6;385(9984):2255-63. doi: 10.1016/S0140-6736(15)60461-5. Epub 2015 Mar 12.

Cummings J, Scheltens P, McKeith I, Blesa R, Harrison JE, Bertolucci PH, Rockwood K, Wilkinson D, Wijker W, Bennett DA, Shah RC. Effect Size Analyses of Souvenaid in Patients with Alzheimer's Disease. J Alzheimers Dis. 2017;55(3):1131-1139. doi: 10.3233/JAD-160745.

Dubois B, Feldman HH, Jacova C, Dekosky ST, Barberger-Gateau P, Cummings J, Delacourte A, Galasko D, Gauthier S, Jicha G, Meguro K, O'brien J, Pasquier F, Robert P, Rossor M, Salloway S, Stern Y, Visser PJ, Scheltens P. Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS-ADRDA criteria. Lancet Neurol. 2007 Aug;6(8):734-46. doi: 10.1016/S1474-4422(07)70178-3.

van Wijk N, Broersen LM, de Wilde MC, Hageman RJ, Groenendijk M, Sijben JW, Kamphuis PJ. Targeting synaptic dysfunction in Alzheimer's disease by administering a specific nutrient combination. J Alzheimers Dis. 2014;38(3):459-79. doi: 10.3233/JAD-130998.

• Responsible Party: Miia Kivipelto, Professor, Karolinska Institutet
• ClinicalTrials.gov Identifier: NCT03249688
• Other Study ID Numbers: E0750301
• First Posted: August 15, 2017
• Last Update Posted: September 23, 2021
• Last Verified: September 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Miia Kivipelto, Karolinska Institutet:

Lifestyle intervention; Medical food; Randomized controlled trial; Prodromal Alzheimer's disease; Prevention; Intervention; Multidomain; Multimodal

Additional relevant MeSH terms:

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