Calorie Restriction and Brain Function in Mild Cognitive Impairment

NCT03872375 | Completed DMC

• 2 other identifiers: 201612732R00AG047282
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 2

Brief Summary

Problems with blood sugar metabolism (i.e., metabolic dysfunction) progressively develop through old age, which is primarily due to obesity and lack of physical activity. Metabolic dysfunction increases the risk for Alzheimer's disease (AD) and negatively impacts memory and related brain function. There is intense interest in developing interventions, particularly non-drug therapies, to combat AD. Recent clinical trials have found that intranasal insulin, which facilitates glucose metabolism in the brain, is able to maintain memory in participants with Mild Cognitive Impairment (MCI), the precursor to AD. While intranasal insulin is a useful, proof-of-concept intervention, it does not affect visceral fat mass and therefore metabolic dysfunction will persist in a given person. The investigators wish to engage participants with MCI in intermittent calorie restriction (CR), to reduce metabolic dysfunction and improve glucose metabolism. Intermittent calorie restriction in this case refers to eating whatever one wants for 5 days, followed by 2 consecutive days of consuming 530 calories via one protein shake with sufficient nutrients to sustain the person. This results in reliable weight loss, which itself improves glucose metabolism in the body and has a wealth of other benefits. (It should be mentioned here that weight maintenance has been shown in studies when participants restrict to 1 day/week).

Conditions

Mild Cognitive Impairment

Keywords

Executive function; MRI; Memory; 5-2 CR

Outcome Measures

Primary Outcomes (1)

• Body Weight

  % change in BMI (kg/m2)

  16 weeks

Secondary Outcomes (9)

• Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)

  16 weeks

• Functional Magnetic Resonance Imaging memory task activation

  16 weeks

• Functional Magnetic Resonance Imaging executive function task activation

  16 weeks

• Cerebral blood flow

  16 weeks

• Neural network functional connectivity

  16 weeks

Other Outcomes (27)

• Brain volume

  16 weeks

• White matter tract integrity

  16 weeks

• NIH EXAMINER Verbal Fluency 1

  16 weeks

Study Arms (2)

Intermittent Calorie Restriction + Dietary Counseling

EXPERIMENTAL

Participants will be asked to consume a single 530 kilocalorie shake (i.e., "High Calorie" Boost shake) on a given day for two consecutive days each week. Participants will eat ad libitum during the remaining 5 days. Participants will also receive Registered Dietitian of Nutrition (RDN) consultations about dietary modifications to induce moderate weight loss. Participants will utilize these recommendations in addition to shake consumption. Subjects are also asked to follow RDN dietary recommendations.

Dietary Supplement: Meal-Replacement Therapy; Behavioral: Dietary Counseling

Dietary Counseling

ACTIVE COMPARATOR

A Registered Dietitian of Nutrition (RDN) will consult with subjects about dietary modifications to induce moderate weight loss. Participants will utilize these recommendations.

Behavioral: Dietary Counseling

Interventions

Meal-Replacement Therapy DIETARY_SUPPLEMENT

The meal replacement shake, consumed once per day on two consecutive days, will over a given week lead to negative energy balance and induce weight loss.

Intermittent Calorie Restriction + Dietary Counseling

Dietary Counseling BEHAVIORAL

A Registered Dietitian of Nutrition will provide consultation on how to induce moderate weight loss.

Dietary Counseling; Intermittent Calorie Restriction + Dietary Counseling

Eligibility Criteria

• Age: 70 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Years of age 70-85;
• Body Mass Index =\> 28 and \< 40 and weight \< 350 pounds;
• Mini-Mental State Examination \>= 24;
• A subjective memory concern from the participant, caregiver/informant, or a clinician;
• An education-adjusted score for the Logical Memory II, paragraph A Wechsler Scale (16 years: 8-10; 8-15 years: 5-7; \< 0-7 years: 2-3);
• A Clinical Dementia Rating - sum of boxes = 0.5;
• No deficits in activities of daily living;
• Consensus confirmation of MCI by senior investigators;
• An informant/caregiver that is informed about the study and will be present at study visits.

You may not qualify if:

• A history of a major cardiovascular event(e.g., heart attack);
• A history of cerebrovascular or other neurological disorders (e.g., stroke, epilepsy, multiple sclerosis, etc.);
• A history of substance abuse in the past 6 months;
• A history of eating disorders;
• A history of clinically significant endocrine disorders (e.g., hypothyroidism);
• A history of mood and anxiety disorders (e.g., Major Depressive Disorder, Generalized Anxiety Disorder, Bipolar disorder, etc.);
• Taking insulin;
• Current use of systemic corticosteroids;
• Current use of Warfarin;
• Having smoked tobacco products in the last 3 months;
• Contraindications for MRI (pacemakers, ferrous metal implants or shrapnel about the face or eyes, etc.);
• Other medical history that, in the opinion of the investigators, would constitute risk for subject participation;
• Hypertension, defined by a diastolic/systolic blood pressure of \> 160/110;
• No current use of memantine or other Alzheimer's disease drugs.

Sponsors & Collaborators

• Iowa State University: lead
• National Institute on Aging (NIA): collaborator

Study Sites (2)

Nutrition and Wellness Research Center

Ames, Iowa, 50011, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

MeSH Terms

Conditions

Cognitive Dysfunction

Interventions

Nutrition Assessment

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Epidemiologic Measurements; Public Health; Environment and Public Health

Study Officials

• Auriel A Willette

  Iowa State University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: All research assistants and senior staff involved in data collection and analysis will be blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Dietary Supplement: Meal-Replacement Therapy To examine the effect of meal-replacement therapy on weight loss, behavior, and brain outcomes in overweight to obese aged adults with mild cognitive impairment.

Study Record Dates

• First Submitted: March 11, 2019
• First Posted: March 13, 2019
• Study Start: May 8, 2019
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: March 31, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)