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

NCT ID: NCT05480358

Last Updated: 2022-07-29

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-01
• Study Completion Date: 2023-08-31

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.

Detailed Description

Cognitive impairment that exceeds the physiological decline associated with aging can take the form of mild cognitive impairment (MCI) or, in its most severe form, dementia. In turn, patients diagnosed with MCI evolve towards outright Alzheimer's disease (AD) in an estimated percentage of 15%/year. MCI can occur in the form of amnestic MCI (amnestic MCI, aMCI; by far the most common) or non-amnestic MCI (single or multiple domain), where amnestic is the form that most frequently evolves into AD. Therefore this clinical trial will focus on the latter (as well as on the AD). Diet cycles with low sugar and protein levels followed by diets with normal levels of these lead to temporary reductions in growth hormone and IGF-1 levels. Both are potential mediators of the neuroprotective and regenerative effects of these diets not only in mice, but also in monkeys and humans . However, heavily restricted diets in terms of calories are often difficult to endure over time and are frequently associated with side effects, even significant ones and with progressive weight loss, in particular of lean mass. In a mouse model of AD, it has been shown that periodic cycles of a "fasting-mimicking" diet (FMD) restricted in protein content (PR-FMD) but not in terms of calories are able to reduce levels plasma levels of IGF-1 with contrasting effects on the neurodegeneration process. In particular, such FMD has been shown to reduce by about 30-70%, the levels of hyperphosphorylated tau protein (one of the typical markers of AD) at the hippocampal level, reducing the age-related deficit of cognitive performance. A relevant neuroregenerative effect (associated with a clinical improvement in motor coordination and memory) has been demonstrated in mice subjected to a diet based on a similar DMD during their "average life" (months 16-30).

It is proposed to conduct a study of twelve monthly cycles of the ProlonADTM diet (by L-Nutra) in patients with aMCI or mild AD (MMSE 18-23) diagnosed according to the criteria defined by Peterson and McKahn, respectively (1, 3 ).

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). Patients in the treatment group alone will also receive a range of supplements containing omega-3 fatty acids, caffeine, tree nuts, coconut oil, olive oil and cocoa - which will be supplied with the ProlonADTM diet kit. Patients assigned to both arms will also receive personalized dietary recommendations matched to instructions for light-moderate physical activity to be carried out also at home and aimed, especially in the case of patients assigned to receive ProlonADTM, to prevent the loss of lean mass. The primary endpoint of the study will be the feasibility and safety of the twelve cycles of ProlonADTM. Feasibility is defined as taking at least one course of DMD every two months with the option of admitting consumption of 50% of the planned diet and / or a maximum consumption of 10 Kcal / kg of unforeseen food in only one of days 1-5 of each cycle. Investigators speculate that ProlonADTM will not cause severe side effects and that it will have no detrimental effect on the patient's body composition, specifically in terms of impact on lean mass measured by dynamometry and bioimpedance analysis.

Secondary objectives will include:

• conversion rate to AD (for patients with aMCI);
• episodic memory evaluated with Free and Cued Selective Reminding Test (FCRST);
• cognitive status assessed by MMSE, CDR-Sum of the boxes;
• functional status assessed with Barthel Index, IADL;
• emotional state assessed using the CESD-R scale;
• nutritional status (MNA and body composition - bioimpedance, handgrip);
• caregiver stress assessed through Caregiver Burden Inventory and NPI;
• quality of life of patients (QLQ-AD);
• inflammatory markers, oxidative stress markers, neuronal damage markers (Neurofilament Light, NfL), quantification of circulating stem cells, cell aging markers (eg evaluation of the telomerase activity of lymphocytes).
• assessment of frailty (Rockwood frailty index, which also includes walking speed, handgrip, breathing capacity)

Conditions

Mild Cognitive Impairment; Mild Dementia; Fasting-Mimicking Diet

Keywords

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

ProlonADTM

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.

Group Type: EXPERIMENTAL

Fasting-Mimicking Diet ProlonADTM

Intervention Type: 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

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

Group Type: PLACEBO_COMPARATOR

Fasting-Mimicking Diet ProlonADTM

Intervention Type: 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.

Interventions

Fasting-Mimicking Diet ProlonADTM

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.

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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.

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Genova

OTHER

Sponsor Role: lead

Responsible Party

Alessio Nencioni

Full Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Alessio Nencioni

Genoa, GE, Italy

Site Status: RECRUITING

Ospedale Policlinico San Martino

Genova, , Italy

Site Status: RECRUITING

Azienda Ospedaliera di Perugia

Perugia, , Italy

Site Status: RECRUITING

Countries

Italy

Facility Contacts

Alessio Nencioni, MD

Role: primary

Alessio Nencioni

Role: primary

Patrizia Mecocci

Role: primary

References

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.

Reference Type: DERIVED

PMID: 36170815 (View on PubMed)

Other Identifiers

FMD AD

Identifier Type: -

Identifier Source: org_study_id