Chocolate and Physical Exercise to Reduce Malnutrition in Pre-dementia Aged People

NCT05343611 | Unknown

• 1 other identifier: JPI- ERAHDL
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 4

Brief Summary

We hypothesize that the antioxidant and cytoprotective functions of vitamin E combined with the cortisol-lowering effect of chocolate polyphenols and physical activity may help prevent the age-dependent decline of mitochondrial function and nutrient metabolism in skeletal muscle, key underpinning events in protein-energy malnutrition (PEM) and muscle wasting in the elderly. To test this hypothesis, a vitamin E functionalized dark chocolate rich in polyphenols will be developed with the collaboration of Nestlè Company, and its effects will be investigated combined with physical activity in a 6-month randomized case-control trial on pre-dementia elderly patients, a well-defined population of subjects at risk of undernutrition and frailty. Subjects stabilized on a protein-rich diet (0.9-1.0 g protein/Kg ideal body weight/day) and physical exercise program (High Intensity Interval Training specifically developed for these subjects), will be randomized in 3 groups (n = 34 each): controls (Group A) will maintain the baseline diet and cases will receive either 30 g/day of dark chocolate containing 500 mg total polyphenols (corresponding to 60 mg epicatechin) and 100 mg vitamin E (as RRR-alpha-tocopherol) (Group B) or the high polyphenol chocolate without additional vitamin E (Group C). Diet will be isocaloric and with the same intake of polyphenols and vitamin E in the 3 groups. Muscle mass will be the primary endpoint and other clinical endpoints will include neurocognitive status and previously identified biomolecular indices of frailty in pre-dementia patients. Muscle biopsies will be collected to assess myocyte contraction and mitochondrial metabolism. Laboratory endpoints will include the nutritional compliance to the proposed intervention (blood polyphenols and vitamin E status and metabolism), 24-h salivary cortisol, steroid hormones and IGF-1, and molecular indices of inflammation, oxidant stress, cell death and autophagy. These parameters will be investigated in muscle and blood cells by state-of-the-art omics techniques. Molecular and nutritional findings will also be confirmed in vitro using skeletal myotubes, blood leukocytes and neural cell lines. Clinical and laboratory results will be processed by a dedicated bioinformatics platform (developed with the external collaboration of the omics company Molecular Horizon Srl) to interpret the molecular response to the nutritional intervention and to personalize its application.

Conditions

Dementia; Dementia, Mild; Dementia Moderate; Dementia Senile; Malnutrition; Deficiency Nutritional; Deficiency Diseases

Keywords

Frailty; Physical Exercise; Undernutrition; Protein deficiency; Chocolate; Vitamin E; Phenols

Outcome Measures

Primary Outcomes (1)

• Change in free-fat soft tissue mass (g)

  Change in free-fat soft tissue mass, (FFSTM, g), will be assessed by means of a whole-body scan on a dual-energy X-ray absorptiometry scanner. Values at the regional level (upper limbs, lower limbs and trunk) will be also considered.

  Baseline (T00), Pre-intervention (T0) after 2-4 weeks, Mid-intervention (T1) after 3 months, Post-intervention (T2) after 3 months and Follow-up (T3) after 3 months

Secondary Outcomes (25)

• Change in Quadriceps volume and cross-sectional area

  Pre-intervention (T0), Mid-intervention (T1) after 3 months, Post-intervention (T2) after 3 months and Follow-up (T3) after 3 months

• Change in the torque (Nm) and rate of torque development (Nm/s) of quadriceps during Maximal Voluntary Activation and electrically evoked potential

  Baseline (T00), Pre-intervention (T0) after 2-4 weeks, Mid-intervention (T1) after 3 months, Post-intervention (T2) after 3 months and Follow-up (T3) after 3 months

• Change in the one repetition maximum load (kg)

  Baseline (T00), Pre-intervention (T0) after 2-4 weeks, Mid-intervention (T1) after 3 months, Post-intervention (T2) after 3 months and Follow-up (T3) after 3 months

• Change in the Rate of Force Development (N/s)

  Baseline (T00), Pre-intervention (T0) after 2-4 weeks, Mid-intervention (T1) after 3 months, Post-intervention (T2) after 3 months and Follow-up (T3) after 3 months

• Change in submaximal and maximal oxygen consumption (ml/kg/min)

  Baseline (T00), Pre-intervention (T0) after 2-4 weeks, Mid-intervention (T1) after 3 months, Post-intervention (T2) after 3 months and Follow-up (T3) after 3 months

Study Arms (3)

Group A (Controls: HPro diet and HIT)

ACTIVE COMPARATOR

Subjects included in this group will serve as controls and will maintain the HPro Diet + HIT program prescribed to all the participants included in the randomization step of the study. The subjects' diet will be adjusted to receive the same overall intake of calories (+ 180 kcal) and macronutrients (+ 3 g of proteins, 4 g of carbohydrates, +11 g of fat, + 4 g of fibers) that the chocolate products will provide to groups B and C.

Behavioral: Combination of High Protein Diet and Physical Exercise protocol

Group B (Case 1: HPP Choko)

SHAM COMPARATOR

Individuals included in this group will undergo the same diet and physical exercise as Group A and additionally they will add to their diet 30g of 85% dark chocolate high in PP (HPP ≥ 500 mg of PP and corresponding to ≥ 60 mg of epicatechin).

Behavioral: Combination of High Protein Diet and Physical Exercise protocol; Dietary Supplement: HPP Choko

Group C (Case 2: HPP/VE Chocolate)

EXPERIMENTAL

Individuals included in this group will undergo the same diet and physical exercise as Group A and additionally they will add to their diet 30 grams of 85% dark HPP chocolate functionalized with 100 mg Vitamin E per day.

Behavioral: Combination of High Protein Diet and Physical Exercise protocol; Dietary Supplement: HPP/VE Choko

Interventions

Combination of High Protein Diet and Physical Exercise protocol BEHAVIORAL

A high Protein Diet (HPro) will be provided to maintain individual caloric endpoint and to adjust protein intake to 0.9-1.0 g/Kg ideal body weight. Each participant will receive a tailored diet (taking into account personal preference) which will follow common general guidelines. Servings of food high in polyphenols will be limited to one per day. Physical exercise will be undertaken three times each week for about 50 minutes per session. The intervention will consist of both aerobic and strength training exercises. Aerobic exercise will consist of walking on a treadmill with 4 x 4 minutes at (85-95% of HRmax), interrupted by 3-minute active recovery periods (60-70% of HRmax). Strength exercise consists of maximal strength training, using a seated leg press with 4 sets of 4 repetitions at \~90% of maximal strength (1RM). Rest periods between the sets will be 3-4 min.

Group A (Controls: HPro diet and HIT); Group B (Case 1: HPP Choko); Group C (Case 2: HPP/VE Chocolate)

HPP Choko DIETARY_SUPPLEMENT

Participants add to their diet with 30 g/day of 85% dark chocolate high in polyphenols

Group B (Case 1: HPP Choko)

HPP/VE Choko DIETARY_SUPPLEMENT

Participants add to their diet 30 grams of 85% dark chocolate high in polyphenols, functionalized with 100 mg of Vitamin E per day.

Group C (Case 2: HPP/VE Chocolate)

Eligibility Criteria

• Age: 65 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Presence of Mild Cognitive Impairment or Mild Dementia. Recruited individuals will be assessed by means of Neuropsychological tests (Mini Mental State Examination, evaluations criteria from Diagnostic and Statistical Manual for Mental Disorder-5) which will be performed by an expert Neuropsychologist

You may not qualify if:

• Presence of kidney or liver failure, or any other liver or kidney disease;
• Presence of gastro-intestinal disorders (i.e. irritable bowel syndrome);
• Presence of food intolerance;
• Presence of heart failure, angina, pulmonary disease, cancer and cancer-related cachexia;
• Presence of coagulation disorders;
• Addictive or previous addictive behaviour, defined as the abuse of cannabis, opioids or other drugs, carrier of infectious diseases;
• Presence of musculoskeletal diseases;
• Suffering from mental illness, inability to cooperate;
• Suffering from known cardiac conditions (e.g. pacemakers, arrhythmias, and cardiac conduction disturbances) or peripheral neuropathy;
• Regular users of any proton pump inhibitors (e.g., omeprazole, lansoprazole, pantoprazole), antibiotics, anticoagulant medication or antiplatelet medications in high dose (es: acetylsalicylic acid \>200mg x day);
• Mini Mental State (MMSE): results \>= 10 points

Sponsors & Collaborators

• Massimo Venturelli, PhD: lead
• University Of Perugia: collaborator
• Instituto de Investigacion Sanitaria INCLIVA: collaborator
• Molde University College: collaborator
• University of Liverpool: collaborator
• Molecular Horizon S.r.l.: collaborator
• Nestlé Italiana S.p.A.: collaborator

Study Sites (4)

CeRiSM (Sport Mountain and Health Research Center)

Rovereto, Trento, 38068, Italy

RECRUITING

Clinica Pederzoli

Peschiera del Garda, Verona, 37019, Italy

RECRUITING

Fondazione Mons. A. Mazzali ONLUS

Mantova, 46100, Italy

RECRUITING

University of Verona

Verona, 37131, Italy

RECRUITING

Related Publications (26)

• Roberts SB, Rosenberg I. Nutrition and aging: changes in the regulation of energy metabolism with aging. Physiol Rev. 2006 Apr;86(2):651-67. doi: 10.1152/physrev.00019.2005.

  PMID: 16601270 BACKGROUND

• Anderson RM, Weindruch R. Metabolic reprogramming, caloric restriction and aging. Trends Endocrinol Metab. 2010 Mar;21(3):134-41. doi: 10.1016/j.tem.2009.11.005. Epub 2009 Dec 7.

  PMID: 20004110 BACKGROUND

• Grassi D, Lippi C, Necozione S, Desideri G, Ferri C. Short-term administration of dark chocolate is followed by a significant increase in insulin sensitivity and a decrease in blood pressure in healthy persons. Am J Clin Nutr. 2005 Mar;81(3):611-4. doi: 10.1093/ajcn/81.3.611.

  PMID: 15755830 BACKGROUND

• Venturelli M, Ce E, Limonta E, Muti E, Scarsini R, Brasioli A, Schena F, Esposito F. Possible Predictors of Involuntary Weight Loss in Patients with Alzheimer's Disease. PLoS One. 2016 Jun 27;11(6):e0157384. doi: 10.1371/journal.pone.0157384. eCollection 2016.

  PMID: 27347878 BACKGROUND

• Venturelli M, Sollima A, Ce E, Limonta E, Bisconti AV, Brasioli A, Muti E, Esposito F. Effectiveness of Exercise- and Cognitive-Based Treatments on Salivary Cortisol Levels and Sundowning Syndrome Symptoms in Patients with Alzheimer's Disease. J Alzheimers Dis. 2016 Jul 14;53(4):1631-40. doi: 10.3233/JAD-160392.

  PMID: 27540967 BACKGROUND

• Cavedon V, Milanese C, Laginestra FG, Giuriato G, Pedrinolla A, Ruzzante F, Schena F, Venturelli M. Bone and skeletal muscle changes in oldest-old women: the role of physical inactivity. Aging Clin Exp Res. 2020 Feb;32(2):207-214. doi: 10.1007/s40520-019-01352-x. Epub 2019 Sep 18.

  PMID: 31535334 BACKGROUND

• Helgerud J, Hoydal K, Wang E, Karlsen T, Berg P, Bjerkaas M, Simonsen T, Helgesen C, Hjorth N, Bach R, Hoff J. Aerobic high-intensity intervals improve VO2max more than moderate training. Med Sci Sports Exerc. 2007 Apr;39(4):665-71. doi: 10.1249/mss.0b013e3180304570.

  PMID: 17414804 BACKGROUND

• Wang E, Naess MS, Hoff J, Albert TL, Pham Q, Richardson RS, Helgerud J. Exercise-training-induced changes in metabolic capacity with age: the role of central cardiovascular plasticity. Age (Dordr). 2014 Apr;36(2):665-76. doi: 10.1007/s11357-013-9596-x. Epub 2013 Nov 16.

  PMID: 24243396 BACKGROUND

• Storen O, Helgerud J, Saebo M, Stoa EM, Bratland-Sanda S, Unhjem RJ, Hoff J, Wang E. The Effect of Age on the V O2max Response to High-Intensity Interval Training. Med Sci Sports Exerc. 2017 Jan;49(1):78-85. doi: 10.1249/MSS.0000000000001070.

  PMID: 27501361 BACKGROUND

• Wisloff U, Stoylen A, Loennechen JP, Bruvold M, Rognmo O, Haram PM, Tjonna AE, Helgerud J, Slordahl SA, Lee SJ, Videm V, Bye A, Smith GL, Najjar SM, Ellingsen O, Skjaerpe T. Superior cardiovascular effect of aerobic interval training versus moderate continuous training in heart failure patients: a randomized study. Circulation. 2007 Jun 19;115(24):3086-94. doi: 10.1161/CIRCULATIONAHA.106.675041. Epub 2007 Jun 4.

  PMID: 17548726 BACKGROUND

• Sumiyoshi E, Matsuzaki K, Sugimoto N, Tanabe Y, Hara T, Katakura M, Miyamoto M, Mishima S, Shido O. Sub-Chronic Consumption of Dark Chocolate Enhances Cognitive Function and Releases Nerve Growth Factors: A Parallel-Group Randomized Trial. Nutrients. 2019 Nov 16;11(11):2800. doi: 10.3390/nu11112800.

  PMID: 31744119 BACKGROUND

• Smith DF. Benefits of flavanol-rich cocoa-derived products for mental well-being: A review. Journal of Functional Foods. 2013; 5 (1): 10-15.

  BACKGROUND

• Mao T, Van De Water J, Keen CL, Schmitz HH, Gershwin ME. Cocoa procyanidins and human cytokine transcription and secretion. J Nutr. 2000 Aug;130(8S Suppl):2093S-9S. doi: 10.1093/jn/130.8.2093S.

  PMID: 10917928 BACKGROUND

• Tsang C, Hodgson L, Bussu A, Farhat G, Al-Dujaili E. Effect of Polyphenol-Rich Dark Chocolate on Salivary Cortisol and Mood in Adults. Antioxidants (Basel). 2019 May 29;8(6):149. doi: 10.3390/antiox8060149.

  PMID: 31146395 BACKGROUND

• Isanejad M, Mursu J, Sirola J, Kroger H, Rikkonen T, Tuppurainen M, Erkkila AT. Dietary protein intake is associated with better physical function and muscle strength among elderly women. Br J Nutr. 2016 Apr 14;115(7):1281-91. doi: 10.1017/S000711451600012X. Epub 2016 Feb 9.

  PMID: 26857389 BACKGROUND

• Sastre J, Pallardo FV, Pla R, Pellin A, Juan G, O'Connor JE, Estrela JM, Miquel J, Vina J. Aging of the liver: age-associated mitochondrial damage in intact hepatocytes. Hepatology. 1996 Nov;24(5):1199-205. doi: 10.1002/hep.510240536.

  PMID: 8903398 BACKGROUND

• Miller CJ, Gounder SS, Kannan S, Goutam K, Muthusamy VR, Firpo MA, Symons JD, Paine R 3rd, Hoidal JR, Rajasekaran NS. Disruption of Nrf2/ARE signaling impairs antioxidant mechanisms and promotes cell degradation pathways in aged skeletal muscle. Biochim Biophys Acta. 2012 Jun;1822(6):1038-50. doi: 10.1016/j.bbadis.2012.02.007. Epub 2012 Feb 15.

  PMID: 22366763 BACKGROUND

• McArdle A, Jackson MJ. Exercise, oxidative stress and ageing. J Anat. 2000 Nov;197 Pt 4(Pt 4):539-41. doi: 10.1046/j.1469-7580.2000.19740539.x.

  PMID: 11197526 BACKGROUND

• Galli F, Azzi A, Birringer M, Cook-Mills JM, Eggersdorfer M, Frank J, Cruciani G, Lorkowski S, Ozer NK. Vitamin E: Emerging aspects and new directions. Free Radic Biol Med. 2017 Jan;102:16-36. doi: 10.1016/j.freeradbiomed.2016.09.017. Epub 2016 Nov 2.

  PMID: 27816611 BACKGROUND

• Wu D, Meydani SN. Age-associated changes in immune function: impact of vitamin E intervention and the underlying mechanisms. Endocr Metab Immune Disord Drug Targets. 2014;14(4):283-9. doi: 10.2174/1871530314666140922143950.

  PMID: 25244230 BACKGROUND

• Khor SC, Abdul Karim N, Ngah WZ, Yusof YA, Makpol S. Vitamin E in sarcopenia: current evidences on its role in prevention and treatment. Oxid Med Cell Longev. 2014;2014:914853. doi: 10.1155/2014/914853. Epub 2014 Jul 6.

  PMID: 25097722 BACKGROUND

• Chung E, Mo H, Wang S, Zu Y, Elfakhani M, Rios SR, Chyu MC, Yang RS, Shen CL. Potential roles of vitamin E in age-related changes in skeletal muscle health. Nutr Res. 2018 Jan;49:23-36. doi: 10.1016/j.nutres.2017.09.005. Epub 2017 Sep 21.

  PMID: 29420990 BACKGROUND

• Schubert M, Kluge S, Schmolz L, Wallert M, Galli F, Birringer M, Lorkowski S. Long-Chain Metabolites of Vitamin E: Metabolic Activation as a General Concept for Lipid-Soluble Vitamins? Antioxidants (Basel). 2018 Jan 12;7(1):10. doi: 10.3390/antiox7010010.

  PMID: 29329238 BACKGROUND

• Bartolini D, De Franco F, Torquato P, Marinelli R, Cerra B, Ronchetti R, Schon A, Fallarino F, De Luca A, Bellezza G, Ferri I, Sidoni A, Walton WG, Pellock SJ, Redinbo MR, Mani S, Pellicciari R, Gioiello A, Galli F. Garcinoic Acid Is a Natural and Selective Agonist of Pregnane X Receptor. J Med Chem. 2020 Apr 9;63(7):3701-3712. doi: 10.1021/acs.jmedchem.0c00012. Epub 2020 Mar 20.

  PMID: 32160459 BACKGROUND

• Wong SH, Knight JA, Hopfer SM, Zaharia O, Leach CN Jr, Sunderman FW Jr. Lipoperoxides in plasma as measured by liquid-chromatographic separation of malondialdehyde-thiobarbituric acid adduct. Clin Chem. 1987 Feb;33(2 Pt 1):214-20.

  PMID: 3802504 BACKGROUND

• Pedrinolla A, Isanejad M, Antognelli C, Bartolini D, Borras C, Cavedon V, Di Sante G, Migni A, Mas-Bargues C, Milanese C, Baschirotto C, Modena R, Pistilli A, Rende M, Schena F, Stabile AM, Telesa NV, Tortorella S, Hemmings K, Vina J, Wang E, McArdle A, Jackson MJ, Venturelli M, Galli F. Randomised controlled trial combining vitamin E-functionalised chocolate with physical exercise to reduce the risk of protein-energy malnutrition in predementia aged people: study protocol for Choko-Age. BMJ Open. 2023 Dec 22;13(12):e072291. doi: 10.1136/bmjopen-2023-072291.

  PMID: 38135320 DERIVED

MeSH Terms

Conditions

Dementia; Lymphoma, Follicular; Alzheimer Disease; Malnutrition; Deficiency Diseases; Frailty; Motor Activity; Protein Deficiency

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Tauopathies; Neurodegenerative Diseases; Nutrition Disorders; Nutritional and Metabolic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Behavior

Study Officials

• Massimo Venturelli, PhD

  Universita di Verona

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Roberto Modena, PhD

CONTACT

00390464483508; roberto.modena@univr.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: April 11, 2022
• First Posted: April 25, 2022
• Study Start: May 1, 2022
• Primary Completion: December 30, 2024
• Study Completion: December 30, 2024
• Last Updated: June 23, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: The availability period will start immediately following the publication and will not end.
• Access Criteria: The IPD will be shared with Researchers who provide a methodologically sound proposal to achieve this proposal's aims and for IPD meta-analysis. Request and proposal have to be sent to francesco.galli@unipg.it and massimo.venturelli@univr.it.

Locations

IT (4)