Characterisation of Functional and Cognitive Responses Following Olfactory Stimulation and/or Functional Training in Older Adults. (INNOLFACT 2)

Characterisation of Functional and Cognitive Responses Following Olfactory Stimulation and/or Functional Training in Older Adults: A Randomised Clinical Trial

This randomized controlled trial will evaluate the effects of olfactory stimulation and/or multicomponent physical training in adults aged 60 years and older. Eligible participants will be cognitively normal, community-dwelling outpatients recruited from Primary Care and Geriatrics services. After baseline assessment, participants will be randomized to one of four groups: usual care, olfactory training/stimulation, multicomponent physical exercise, or combined olfactory and exercise intervention.

Primary and secondary assessments will include olfactory function, cognition, physical function, quality of life, nutritional status, mood, frailty, multimorbidity, polypharmacy, blood-based molecular biomarkers, and exhaled-air biomarkers.

Study Overview

• Status: Completed
• Conditions: Frailty; Healthy Aging; Cognitive Decline; Olfactory Dysfunction; Physical Performance Decline in Older Adults
• Intervention / Treatment: Other: Olfactory stimulation; Other: Multicomponent physical training; Other: Combined olfactory stimulation and multicomponent physical training

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Navarre
    • Pamplona, Navarre, Spain
      • Hospital Universitario de Navarra

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria

• Adults aged ≥60 years under the care of Primary Care and/or the Geriatrics Service of the Hospital Universitario de Navarra;
• Normal cognitive function as determined at baseline assessment (Mini-Mental State Examination [MMSE] score ≥23; ≥21 for individuals without formal education);
• Fluent in speaking, reading, and understanding Spanish;
• Adequate olfactory function;
• Adequate visual and auditory acuity to complete neuropsychological and computerized assessments;
• In good general health, with no condition expected to interfere with study participation;
• Willing and able to comply with study procedures and to participate for the entire study duration;
• Willing to refrain from the use of scented candles, essential oils, or air fresheners during study participation.

Exclusion Criteria

• Refusal or inability of the participant, primary caregiver, or legal representative to provide informed consent;
• Diagnosis of a neurodegenerative disease or severe dementia (Global Deterioration Scale [GDS] stage 6-7);
• Conditions affecting the olfactory system (e.g., nasal polyps);
• Life expectancy <3 months;
• History of asthma, allergies, or olfactory-triggered responses producing allergy-like symptoms (e.g., rhinorrhea, lacrimation, sneezing, or skin rash);
• History of neurological disorders such as Parkinson's disease, multiple sclerosis, brain cyst, tumor, or aneurysm;
• Significant medical conditions, including uncontrolled diabetes mellitus, uncontrolled hypertension, nutritional deficiencies, or thyroid disorders;
• History of major psychiatric disorders such as schizophrenia, bipolar disorder, anxiety disorders, or attention-deficit/hyperactivity disorder;
• History of alcohol or substance abuse or dependence within the past 2 years (DSM-IV criteria), including use of cigarettes, e-cigarettes, cigars, marijuana, or any substance that may produce odors interfering with the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control group.; Participants assigned to the control group will receive usual care and will not undergo any specific intervention related to olfactory or physical training during the study period.
Experimental: Olfactory stimulation intervention.; Participants assigned to this group will undergo a structured olfactory stimulation program (overnight olfactory enrichment) aimed at improving or maintaining olfactory and congnitive function through repeated exposure to selected odors over the intervention period.	Other: Olfactory stimulation; Participants assigned to this group will undergo a structured olfactory stimulation program aimed at improving or maintaining olfactory and cognitive function through repeated and exposure to selected odors over the intervention period.; Other Names: Group 1
Experimental: Multicomponent physical training intervention.; Participants in this group will take part in a multicomponent physical training program including exercises targeting strength, balance, and aerobic capacity, adapted to older adults and conducted following established safety guidelines.	Other: Multicomponent physical training; Participants in this group will take part in a multicomponent physical training program including exercises targeting strength, balance, and aerobic capacity, adapted to older adults and conducted following established safety guidelines.; Other Names: Group 2
Experimental: Combined olfactory training/stimulation and multicomponent physical training intervention.; Participants assigned to this group will receive a combined intervention consisting of both the olfactory stimulation program and the multicomponent physical training program, delivered concurrently during the study period.	Other: Combined olfactory stimulation and multicomponent physical training; Participants assigned to this group will receive a combined intervention consisting of both the olfactory stimulation program and the multicomponent physical training program, delivered concurrently during the study period.; Other Names: Group 3

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive Function	Changes in Cognitive Function assessed with Mini-Mental State Examination (30-point questionnaire; scale of 0 [worst] to 30 [best]).	Baseline and Day 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Olfactory Function (Sniffin' Sticks Test - TDI Score)	Olfactory performance will be assessed using the Sniffin' Sticks Test (SST), providing a composite Threshold, Discrimination, and Identification (TDI) score. Odorants will be presented using CE-marked pen devices approximately 2 cm in front of both nostrils for 2 seconds. The Sniffin Sticks Score ranges from 0 (worst) to 48 (best). Normative values: less than or equal 15 = Functional Anosmia; 16 - 30 = Hyposmia; 31 - 48 = Normosmia.	Baseline and Day 30
Physical Function	Physical Function: Assessed using the Short Physical Performance Battery (SPPB), which combines balance, gait velocity, and leg strength as a single score on a 0 (worst) to 12 (best scale).	Baseline and Day 30
Mini-Cog - Quick Screening for early dementia detection	Mini-Cog (5-point abreviated spanish version, the total score combines word recall (3 points) and a clock drawing task (2 points).	Baseline and day 30
Quality of life (QoL)	Measurment of quality of life using EQ5D-3L, the patients indicate their health state by choosing one level for each of the five dimensions, creating a 5-digit code representing 243 possible health states. EQ VAS, includes a vertical Visual Analogue Scale (0-100) where patients rate their self-rated health, with 100 being the "best imaginable health state". Utility. The responses can be converted into a single index value (utility score) using country-specific valuation sets, where 1 represents full health and 0 represents death.	Baseline and Day 30
Nutritional Status	Mini Nutritional Assessment (MNA) ranges from normal nutritional status (24-30points), risk of malnutrition (17-23.5points), or malnourished (<17points).	Baseline and Day 30
Barthel Index	Barthel Index of independence during activities of daily living (ADLs) ranges from 0 (severe functional dependence) to 100 (functional independence).	Baseline to Day 30
Blood Biomarkers	Blood samples (10-20 mL) will be collected alongside routine clinical testing using Vacutainer tubes (EDTA, citrate, or serum tubes as appropriate). Samples will be left upright for 10 minutes and centrifuged at 3000 rpm for 15 minutes to obtain serum and plasma for analysis. Aliquots will be stored at -80°C for future specialised analyses, including flow cytometry. Remaining samples will be stored in the Navarrabiomed Biobank for future research, subject to Ethics Committee approval.	Baseline and Day 30
Mood state	Yesavage Geriatric Depression Scale (GDS-15, short form) is a validated screening tool designed to detect and assess depresive symtoms specifically in older adults. The scale ranges from 0 (best) to 15 (worst). The reference scoring for the Short Form (GDS-15) is: 0-5 = Normal; 6-9 = Mild or posible Depression; >9 = Established/Severe Depression.	Baseline an Day 30
Symbol Digit Modalities Test (SDMT)	Symbol Digit Modalities Test (SDMT) measures cognitive processing speed, attention, and memory by having participants pair symbols with numbers (1-9) using a key, with a maximum score of 110-120 over 90 seconds. A 4-point difference in SDMT scores is considered clinically meaningful, often used to detect cognitive dysfunction.	Baseline and Day 30
Trail Making Test - part A	Trail Making Test Part A is scored by measuring the total time in seconds required to connect 25 numbered circles (an average completion time is 29 seconds, with >78 seconds often indicating cognitive impairment - Scores are often adjusted based on age, education, and user-specific norms).	Baseline and day 30
Multimorbidity	Assessed using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G) alongside ICD-10 classification provides a robust, comprehensive, and validated method for assessing multicomorbidity in older adults, addressing both the structural burden of disease and its functional severity. Total scores can range from 0 to 64. The CIRS-G Severity Index (total score divided by the number of organ systems involved) provides an estimate of the overall severity of dysfunction. System Coverage rates 14 organ systems (e.g., cardiac, vascular, respiratory, psychiatric) on a severity scale from 0 (no problem) to 4 (Extremely severe).	Baseline and Day 30
Strength	Handgrip strength and maximal concentric strength (leg press, chest press, knee extension, seated row machine). Changes in "1RM", defined as the maximum resistance/load a person can move in one repetition of an exercise will be assessed. These values are mesured in Kilograms and results are individualized.	Baseline an Day 30
Medication Use (Polypharmacy and Psychotropic Drugs)	Number and type of medications will be recorded. Polypharmacy will be defined as the use of ≥5 medications. Psychotropic drug use and medications related to comorbid or intercurrent conditions (e.g., antibiotics) will also be documented	Baseline and Day 30
Exhaled Air Biomarkers (FeNO)	Fractional exhaled nitric oxide (FeNO) will be measured as a non-invasive biomarker of airway inflammation and as a potential indicator of muscle function, inflammatory status, frailty, and sarcopenia. Measurements will be performed using a CE-marked device currently used in routine clinical practice for asthma management. The study aims to evaluate its utility for monitoring intervention effects and for early diagnosis, prognosis, and follow-up of frailty and cognitive decline.	Baseline and Day 30

Collaborators and Investigators

• Sponsor: Fundacion Miguel Servet
• Collaborators: Hospital of Navarra
• Investigators: Principal Investigator: Nicolas Martinez-Velilla, Navarrabiomed-Fundación Miguel Servet-Hospital Universitario de Navarra

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2024
• Primary Completion (Actual): December 4, 2025
• Study Completion (Actual): December 4, 2025

Study Registration Dates

• First Submitted: May 11, 2026
• First Submitted That Met QC Criteria: May 28, 2026
• First Posted (Actual): June 3, 2026

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Cognition; Biomarkers; Older adults; Precision medicine; Geriatrics; Olfactory stimulation; Exhaled nitric oxide; Olfactory trainning; Multicomponent physical exercise
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Neurocognitive Disorders; Cognition Disorders; Pathological Conditions, Signs and Symptoms; Frailty; Cognitive Dysfunction
• Other Study ID Numbers: INNOLFACT 2.0

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No