Clinical Trial of a Low Protein Diet in Patients With Cognitive Impairment

NCT05480358 | Unknown Phase 1

• 1 other identifier: FMD AD
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 3

Brief Summary

The wide-acting effects of Fasting-Mimicking Diets (FMDs) on metabolic, inflammatory and regenerative pathways leading to reduced pathology or risk factors for various diseases in mice and humans, has the potential to be effective against Alzheimer's disease (AD). It is proposed to conduct a randomized clinical trial of twelve monthly cycles of the ProlonADTM diet (by L-Nutra) vs. placebo diet in patients with aMCI or mild AD (MMSE 18-23). The primary endpoint of the study will be the feasibility and safety of the twelve cycles of ProlonADTM.

Conditions

Mild Cognitive Impairment; Mild Dementia; Fasting-Mimicking Diet

Keywords

Fasting-Mimicking Diet; nutritional status; MCI; Alzheimer Disease

Outcome Measures

Primary Outcomes (2)

• Incidence of Treatment-Emergent Adverse Events

  Safety of FMD in terms of percentage of patients experiencing adverse events and/or worsening of nutritional status. To obtain clinical data on safety of the FMD in MCI or AD patients as assessed by percentage of patients (%) experiencing \> grade 3 adverse events and/or a significant decrease in their lean body mass (kg) and/or with a reduction of phase angle \<5° assessed with bio-impedance measurements.

  12 months

• Percentage of patients able to achieve the designated diet regimen

  Feasibility of FMD in terms of percentage of patients able to complete the diet regimen To evaluate the feasibility of the FMD in MCI and AD patients as assessed by the percentage of patients (%) able to achieve the designated diet regimen.

  12 months

Secondary Outcomes (10)

• Efficacy of the FMD in terms of conversion rate to AD

  12 months

• Efficacy of the FMD in terms of functional state

  12 months

• Efficacy of the FMD in terms of emotional state

  12 months

• Efficacy of the FMD in terms of nutritional state

  12 months

• Efficacy of the FMD in terms of caregiver stress' level

  12 months

Study Arms (2)

ProlonADTM

EXPERIMENTAL

The ProlonADTM diet, which will be taken by the patient once a month for 5 days, is a low-calorie and low-protein diet, and provides all the micronutrients necessary to avoid malnutrition. The diet will be performed in twelve consecutive months. The components of the diet will be approximately 30% calorie restricted and 50% protein restricted but supplemented with 50% of the RDA in vitamins and minerals and also supplemented with both nonessential and essential amino acids identified in animal studies to be effective. Prolon by L-Nutra is a medically-designed dietary kit providing the food to eat for five days. Day 1 of Prolon provides \~4600 kJ (11% protein, 46% fat, and 43%carbohydrate), whereas days 2-to-5 provide \~3000 kJ (9% protein, 44% fat, and 47% carbohydrate) per day.

Dietary Supplement: Fasting-Mimicking Diet ProlonADTM

Placebo diet

PLACEBO COMPARATOR

One meal which substitute or lunch or dinner for 5 days, without calories restriction.

Dietary Supplement: Fasting-Mimicking Diet ProlonADTM

Interventions

Fasting-Mimicking Diet ProlonADTM DIETARY_SUPPLEMENT

Prolon by L-Nutra is a medically-designed dietary kit providing the food to eat for five days. Day 1 of Prolon provides \~4600 kJ (11% protein, 46% fat, and 43% carbohydrate), whereas days 2-to-5 provide \~3000 kJ (9% protein, 44% fat, and 47% carbohydrate) per day.

Placebo diet; ProlonADTM

Eligibility Criteria

• Age: 55 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 55-80;
• Presence of aMCI or initial AD (MMSE 18-23);
• Normal organ function (liver and kidney);
• BMI not less than 20 kg/m2;
• Bioimpedance phase angle (PA) \> 5 °;
• Adherence to informed consent

You may not qualify if:

• Age\> 80 years
• Diabetes mellitus;
• Organ impairment (liver, kidney);
• Food allergies to the components of ProlonADTM;
• Patients on therapy with vitamin K antagonist anticoagulants;
• PA \<5 °;
• Patients who live alone or are not adequately supported by the family context;
• Other experimental therapies in progress.

Sponsors & Collaborators

• University of Genova: lead

Study Sites (3)

Alessio Nencioni

Genoa, GE, 16132, Italy

RECRUITING

Ospedale Policlinico San Martino

Genova, Italy

RECRUITING

Azienda Ospedaliera di Perugia

Perugia, Italy

RECRUITING

Related Publications (1)

• Rangan P, Lobo F, Parrella E, Rochette N, Morselli M, Stephen TL, Cremonini AL, Tagliafico L, Persia A, Caffa I, Monacelli F, Odetti P, Bonfiglio T, Nencioni A, Pigliautile M, Boccardi V, Mecocci P, Pike CJ, Cohen P, LaDu MJ, Pellegrini M, Xia K, Tran K, Ann B, Chowdhury D, Longo VD. Fasting-mimicking diet cycles reduce neuroinflammation to attenuate cognitive decline in Alzheimer's models. Cell Rep. 2022 Sep 27;40(13):111417. doi: 10.1016/j.celrep.2022.111417.

  PMID: 36170815 DERIVED

MeSH Terms

Conditions

Cognitive Dysfunction; Alzheimer Disease

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor

Model Details: This is a pilot, double arm randomized and prospective clinical trial assessing feasibility and safety of a 5-day low protein fasting-mimicking diet in pazients affected by Mild Cognitive Impairment or early Alzheimer disease.

Study Record Dates

• First Submitted: October 18, 2021
• First Posted: July 29, 2022
• Study Start: November 1, 2019
• Primary Completion: August 1, 2023
• Study Completion: August 1, 2023
• Last Updated: July 29, 2022

Record last verified: 2022-07

Locations

IT (3)