Clinical trial NCT05841173: Effects of Weight Loss Management on Cognitive Function in Elderly Women With Obesity
Official title: Effects of Weight Loss Management on Cognitive Function in Elderly Obese Women
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Obesity
Cognitive Change
Keywords: Elderly
Obesity
Weight loss
Cognitive Change
Exogenous Ketones
Diet
Physical activity
Lead sponsor: Federal State Budgetary Scientific Institution "Federal Research Centre of Nutrition, Biotechnology
Sponsor class: OTHER
Collaborators: name: Federal Stare Budgetary Scientific Institution, Mental Health Research Center
First posted: 2023-05-03
Enrollment: 200
Sex: FEMALE
Minimum age (years): 60
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective randomised parallel arms double control interventional study
Primary purpose: OTHER

Brief summary: According to studies, the risk of cerebrovascular disease and cognitive decline are associated with age-related changes. In addition, there is data suggesting a relationship between the progression of this pathology and the presence of obesity and associated metabolic disorders. According to to some research, weight loss associated with cognitive function decline. In this regard, the development of effective, applicable in real clinical practice methods of non-drug treatment and prevention of cerebrovascular disorders and age-related cognitive decline in people with obesity and metabolic disorders, who are at high risk, seems to be extremely relevant.

The main goal of the study is to compare the effectiveness of various weight loss approaches and to study their effects on the cognitive functions of elderly obesity women.

Detailed description: The high prevalence of comorbid pathology characterised the elderly and senile population. Particularly, comorbid condition is often based on obesity. Also, an important characteristic of the elderly and senile age is the development of age-related cognitive deficit and progressive decline in cognitive functions, that is detected in 60.8% of people over 65 years old in Russia according to the EVKALIPT study.

The prevalence of obesity in the Russian population reaches 40% among the elderly population. According to studies, the presence of obesity is "paradoxically" associated with less progression of cognitive function loss, and the risk reduction in some populations reaches 40%. However, the sarcopenic obesity is an independent predictor of cognitive impairment in the elderly. Consequently, the therapy of obesity in elderly and senile population faces two important aspects: the risk of muscle loss and the development of sarcopenia and progressive cognitive decline. The described features of this age group are consistent with the well-known "obesity paradox", in which overweight and obesity are associated with longer life expectancy.

The risk of muscle mass reduction and cognitive functions decrease determines the formation of a specialised approach to obesity management in older population. Thus, the setting of softer and longer-term goals with a gradual decrease in body weight is typical. Studies have considered the use of various interventions, so far the combination of diet with exercise has proven effectiveness in muscle mass protection. At the same time, regular exercises reliably protect from cognitive decline. Thereby, the combination of diet and physical activity is considered as a suitable approach to obesity management in the elderly.

Recently, there have also been a number of studies evaluating the effectiveness of the ketogenic diet. This diet pattern is reliably effective in body weight reduction, skeletal muscle mass maintenance, and adipose tissue metabolism improvement in the elderly . Also, the neuroprotective effects of the ketogenic diet have been confirmed by meta-analyses and have made it possible to include it in current guidelines for the prevention and treatment of cognitive impairment. However, the high frequency of negative effects and the associated low adherence limit the possibilities of using this diet, which led to the development of exogenous ketones that allow reaching the levels of blood ketone bodies associated with neuroprotective properties (0.2-0.5 mmol/l) with better portability.

The main goal of the study is to compare the effectiveness of various weight loss approaches and to study their effects on the cognitive functions of elderly obesity women.

Eligibility criteria: Inclusion Criteria:

1. Female;
2. Age 60 and over;
3. BMI 30.0 kg/m2 or more.

Exclusion Criteria:

1. Male;
2. age under 60;
3. BMI \<30.0 kg/m2;
4. patients unable or unwilling to comply with the requirements of the protocol, including the signing of informed consent (inability to give such consent due to mental deficiency or language barrier), as well as non-compliance with the schedule of visits, persons unable to independently make a decision and sign an informed consent;
5. less than 6 months after suffering cardiovascular events, stroke, severe surgical interventions and injuries;
6. alcohol abuse (including chronic pancreatitis of alcoholic etiology) or drug addiction at present or within the last 5 years;
7. history of malignant diseases, regardless of the treatment during the last 5 years;
8. less than 4 weeks after suffering acute infectious and / or inflammatory diseases, after the onset of complete clinical and laboratory remission;
9. pregnancy and lactation;
10. history of allergic reactions to components of the study product and/or placebo or intolerance to components of the study product and/or placebo.

Primary outcomes:
measure: Change from baseline body weight at 12 weeks
timeFrame: Baseline (visit 1) and after 12 weeks (visit 2)
measure: Change from baseline Montreal Cognitive Assessment (MoCa) test scores at 12 weeks
timeFrame: Baseline (visit 1) and after 12 weeks (visit 2)
measure: Change from baseline Trail Making Test (TMT) a&b test scores at 12 weeks
timeFrame: Baseline (visit 1) and after 12 weeks (visit 2)
measure: Change from baseline Word recall test scores at 12 weeks
timeFrame: Baseline (visit 1) and after 12 weeks (visit 2)
measure: Change from baseline Mean response time in the test "Schulte tables" at 12 weeks
timeFrame: Baseline (visit 1) and after 12 weeks (visit 2)
measure: Change from baseline The Stroop Color and Word Test results at 12 weeks
timeFrame: Baseline (visit 1) and after 12 weeks (visit 2)
measure: Change from baseline Verbal fluency test results at 12 weeks
timeFrame: Baseline (visit 1) and after 12 weeks (visit 2)
Secondary outcomes:
measure: Change from baseline fat mass at 12 weeks
timeFrame: Baseline (visit 1) and after 12 weeks (visit 2)
measure: Change from baseline skeletal muscle mass at 12 weeks
timeFrame: Baseline (visit 1) and after 12 weeks (visit 2)
measure: Change from baseline visceral fat at 12 weeks
timeFrame: Baseline (visit 1) and after 12 weeks (visit 2)
measure: Change from baseline total cholesterol serum levels at 12 weeks
timeFrame: Baseline (visit 1) and after 12 weeks (visit 2)
measure: Change from baseline LDL-cholesterol serum levels at 12 weeks
timeFrame: Baseline (visit 1) and after 12 weeks (visit 2)
measure: Change from baseline HOMA-IR (homeostasis model assessment - insulin resistance) index at 12 weeks
timeFrame: Baseline (visit 1) and after 12 weeks (visit 2)
measure: Change from baseline C-reactive protein (CRP) serum levels at 12 weeks
timeFrame: Baseline (visit 1) and after 12 weeks (visit 2)
measure: Change from baseline Tumor Necrosis Factor Alpha (TNFa) serum levels at 12 weeks
timeFrame: Baseline (visit 1) and after 12 weeks (visit 2)
measure: Change from baseline systolic blood pressure (SBP) at 12 weeks
timeFrame: Baseline (visit 1) and after 12 weeks (visit 2)
measure: Change from baseline diastolic blood pressure (DBP) at 12 weeks
timeFrame: Baseline (visit 1) and after 12 weeks (visit 2)
measure: Change from baseline grip strength at 12 weeks
timeFrame: Baseline (visit 1) and after 12 weeks (visit 2)
measure: Change from baseline Six Minute Walk Test distance at 12 weeks
timeFrame: Baseline (visit 1) and after 12 weeks (visit 2)
measure: Change from baseline Hamilton Anxiety Rating Scale at 12 weeks
timeFrame: Baseline (visit 1) and after 12 weeks (visit 2)
measure: Change from baseline Hamilton Depression Rating Scale at 12 weeks
timeFrame: Baseline (visit 1) and after 12 weeks (visit 2)
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Nutrition Clinic of the Federal Research Centre of Nutrition, Biotechnology and Food Safety
Study officials:
affiliation: Deputy Director of the Federal Research Centre of Nutrition, Biotechnology and Food Safety
name: Antonina V. Starodubova, MD, Full PhD
role: STUDY_DIRECTOR
affiliation: Research Fellow of the Federal research Centre of Nutrition, Biotechnology and Food Safety
name: Yurgita R. Varaeva, MD, MRes
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dadarlat-Pop A, Sitar-Taut A, Zdrenghea D, Caloian B, Tomoaia R, Pop D, Buzoianu A. Profile of Obesity and Comorbidities in Elderly Patients with Heart Failure. Clin Interv Aging. 2020 Apr 21;15:547-556. doi: 10.2147/CIA.S248158. eCollection 2020.
citation: Abdoli N, Salari N, Darvishi N, Jafarpour S, Solaymani M, Mohammadi M, Shohaimi S. The global prevalence of major depressive disorder (MDD) among the elderly: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2022 Jan;132:1067-1073. doi: 10.1016/j.neubiorev.2021.10.041. Epub 2021 Nov 4.
citation: Khovasova NO, Vorobyeva NM, Tkacheva ON, Kotovskaya YV, Naumov AV, Selezneva EV, Ovcharova LN. [The prevalence of anemia and its associations with other geriatric syndromes in subjects over 65 years old: data of Russian epidemiological study EVKALIPT]. Ter Arkh. 2022 Jan 15;94(1):24-31. doi: 10.26442/00403660.2022.01.201316. Russian.
citation: Martinchik AN, Laikam KE, Kozyreva NA, Keshabyants EE, Mikhailov NA, Baturin AK, Smirnova EA. [The prevalence of obesity in various socio-demographic groups of the population of Russia]. Vopr Pitan. 2021;90(3):67-76. doi: 10.33029/0042-8833-2021-90-3-67-76. Epub 2021 May 17. Russian.
citation: Hou Q, Guan Y, Yu W, Liu X, Wu L, Xiao M, Lu Y. Associations between obesity and cognitive impairment in the Chinese elderly: an observational study. Clin Interv Aging. 2019 Feb 15;14:367-373. doi: 10.2147/CIA.S192050. eCollection 2019.
citation: Vidyanti AN, Hardhantyo M, Wiratama BS, Prodjohardjono A, Hu CJ. Obesity Is Less Frequently Associated with Cognitive Impairment in Elderly Individuals: A Cross-Sectional Study in Yogyakarta, Indonesia. Nutrients. 2020 Jan 30;12(2):367. doi: 10.3390/nu12020367.
citation: Wang H, Hai S, Liu YX, Cao L, Liu Y, Liu P, Yang Y, Dong BR. Associations between Sarcopenic Obesity and Cognitive Impairment in Elderly Chinese Community-Dwelling Individuals. J Nutr Health Aging. 2019;23(1):14-20. doi: 10.1007/s12603-018-1088-3.
citation: Colleluori G, Villareal DT. Aging, obesity, sarcopenia and the effect of diet and exercise intervention. Exp Gerontol. 2021 Nov;155:111561. doi: 10.1016/j.exger.2021.111561. Epub 2021 Sep 23.
citation: Kokkinidis DG, Armstrong EJ, Giri J. Balancing Weight Loss and Sarcopenia in Elderly Patients With Peripheral Artery Disease. J Am Heart Assoc. 2019 Jul 2;8(13):e013200. doi: 10.1161/JAHA.119.013200. Epub 2019 Jun 29.
citation: Giudici KV, Guyonnet S, Rolland Y, Vellas B, de Souto Barreto P, Nourhashemi F; MAPT/DSA Group. Body Weight Variation Patterns as Predictors of Cognitive Decline over a 5 Year Follow-Up among Community-Dwelling Elderly (MAPT Study). Nutrients. 2019 Jun 18;11(6):1371. doi: 10.3390/nu11061371.
citation: Bosello O, Vanzo A. Obesity paradox and aging. Eat Weight Disord. 2021 Feb;26(1):27-35. doi: 10.1007/s40519-019-00815-4. Epub 2019 Dec 21.
citation: Semlitsch T, Stigler FL, Jeitler K, Horvath K, Siebenhofer A. Management of overweight and obesity in primary care-A systematic overview of international evidence-based guidelines. Obes Rev. 2019 Sep;20(9):1218-1230. doi: 10.1111/obr.12889. Epub 2019 Jul 8.
citation: Petroni ML, Caletti MT, Dalle Grave R, Bazzocchi A, Aparisi Gomez MP, Marchesini G. Prevention and Treatment of Sarcopenic Obesity in Women. Nutrients. 2019 Jun 8;11(6):1302. doi: 10.3390/nu11061302.
citation: Falck RS, Davis JC, Best JR, Crockett RA, Liu-Ambrose T. Impact of exercise training on physical and cognitive function among older adults: a systematic review and meta-analysis. Neurobiol Aging. 2019 Jul;79:119-130. doi: 10.1016/j.neurobiolaging.2019.03.007. Epub 2019 Mar 26.
citation: Ilyas Z, Perna S, A Alalwan T, Zahid MN, Spadaccini D, Gasparri C, Peroni G, Faragli A, Alogna A, La Porta E, Ali Redha A, Negro M, Cerullo G, D'Antona G, Rondanelli M. The Ketogenic Diet: Is It an Answer for Sarcopenic Obesity? Nutrients. 2022 Jan 30;14(3):620. doi: 10.3390/nu14030620.
citation: Buckinx F, Aubertin-Leheudre M. Nutrition to Prevent or Treat Cognitive Impairment in Older Adults: A GRADE Recommendation. J Prev Alzheimers Dis. 2021;8(1):110-116. doi: 10.14283/jpad.2020.40.
citation: McDonald TJW, Cervenka MC. Lessons learned from recent clinical trials of ketogenic diet therapies in adults. Curr Opin Clin Nutr Metab Care. 2019 Nov;22(6):418-424. doi: 10.1097/MCO.0000000000000596.