Analysis of Frailty Syndrome Within the Framework of the Innovation Fund Project PRÄP-GO (ANA-PRÄP-GO)

Frailty Syndrome Clinical Trial

Official title:

Analysis of the Pathophysiology of Frailty Syndrome and Clinical Development of Frailty Within the Framework of the Innovation Fund Project PRÄP-GO (ANA-PRÄP-GO)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04880824
• Other study ID #: ANA-PRAEP-GO
• Status: Recruiting
• Start date: May 19, 2021
• Est. completion date: August 31, 2025

Study information

• Verified date: June 2024
• Source: Charite University, Berlin, Germany
• Contact: Claudia Spies, MD, Prof.
• Phone: +49 30 450 551102
• Email: claudia.spies[@]charite.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The patients included in PRÄP-GO and the corresponding comparison cohorts will be offered to participate in this complementary study in order to be able to carry out a detailed characterization and phenotyping of the frailty complex.

Amendment vote of 08/05/2024: Recruitment extension of Non-frail surgical control group (NFC cohort) until August 31, 2025.

Description:

As part of the innovation fund project PRÄP-GO (EA1/225/19), a multimodal intervention is being conducted in patients with a frailty syndrome. However, the health care research project is limited to evaluating clinical issues only. In order to be able to research further pathophysiological, clinical, psychosocial and work-organizational connections, different groups of participants will be offered the participation in this scientific support program of PRÄP-GO.

The groups of participants in this accompanying program ANA-PRÄP-GO are:

• Randomized study patients with a frailty syndrome of the intervention study PRÄP-GO (PG cohort)

• Non-frail surgical control group (NFC cohort)

• Non-surgical comparison group (NO cohort)

• Participants with health professions (GB cohort)

Additionally, relatives of the patients can be included.

Subprojects are included to reflect research questions of interest in sub groups:

• Success of endoprosthetic implants (clinical outcome and gait pattern after total hip arthroplasty and total knee arthroplasty in frail patients)

• Functional treatment outcome and health-related quality of life after elective spinal surgery in the PG cohort, in the NFC cohort, and in the NO cohort

• Hemodynamic evaluation in patients of the PG and NFC cohort with preoperative abnormal cardiovascular function

• Establishment of a German standard database for 14 CANTAB tests by CANTAB Connect technology

• Aggregated evaluation of the cognitive data of different surgical cohorts from studies carried out at the department of anesthesiology to describe domain-specific changes in the perioperative course

• Perspectives of different health professional groups regarding barriers and facilitators in the implementation of a prehabilitation program and necessary changes in skill, organizational and management, and communication in an interdisciplinary setting

• Perspectives of patients and significant others regarding the organizational pathway of the prehabilitation program

• Frequency, pathophysiology and trajectory of muscle weakness as well as functional impairments of patients admitted to intensive care units of the PG and NFC cohort and their long-term outcomes.

• The gut microbiome as a potential risk factor for perioperative neurocognitive disorders (PNDs) in the elderly

• Evaluation of nutrition data in all cohorts (e.g. adherence to mediterranean diet, nutrition habits, nutritional status, dental status etc.)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1640
• Est. completion date: August 31, 2025
• Est. primary completion date: August 31, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 70 Years and older

Eligibility

PG cohort:

Inclusion criteria

• Consent given and inclusion in PRÄP-GO

• Patient capable of giving consent or existing legal guardian in the case of patients not capable of giving consent

Exclusion criteria

• None

NFC cohort:

Inclusion criteria

• Patient capable of giving consent or existing legal guardian in the case of patients not capable of giving consent

• Age = 70 years

• Elective surgery planned

• Expected anesthesia duration> 60 min

• No frailty syndrome (0 positive out of 5 standardized parameters) according to the physical frailty phenotype (Fried et al., 2001)

Exclusion criteria

• Severe cardiac or pulmonary disease (NYHA IV, Gold IV)

• Intracranial interventions

• Moribund patients (palliative situation)

• Patients with a neuropsychiatric clinical picture or severe hearing and / or visual acuity impairment (not compensated by visual or hearing aids), which limit the performance of the neurocognitive tests

• Insufficient language skills

• Participation in another interventional rehabilitation study or a study according to the German Drug Law or the medical Device Law that has not been approved by the study leader (Exception: parallel participation in adjuvant therapy study).

NO cohort:

Inclusion criteria

• Age = 70 years

• No elective surgery planned

• No surgery within 6 months prior to study enrollment

Exclusion criteria - See NFC cohort

GB cohort:

Inclusion criterion

• Doctor, nurse or therapist from the cooperation partners of PRAEP-GO who were involved in the project

Exclusion criterion

• Language barrier

Relatives:

Inclusion criteria

• Member of a patient in the PRÄP-GO cohort

• Age = 18 years

Exclusion criterion

• Language barrier

Related Conditions & MeSH terms

• Frailty
• Frailty Syndrome
• Syndrome

Intervention

Behavioral:
• Prehabilitation- new form of care
The participants in the intervention group take part in a shared decision-making (SDM) conference to plan the intervention. The therapeutic content of the prehabilitation is defined individually for each patient in the SDM conference. Prehabilitation will be a structured and individually tailored 3-week program.

Locations

Country	Name	City	State
Germany	Auguste-Viktoria-Klinikum - Vivantes - Netzwerk für Gesundheit GmbH	Berlin
Germany	CARITAS Klinik Maria Heimsuchung	Berlin
Germany	Charité-Universitätsmedizin Berlin, Department of Physical Medicine	Berlin
Germany	Department of Anesthesiology and Intensive Care Medicine, Charité - University Medicine	Berlin
Germany	Department of Anesthesiology and Operative Intensive Care Medicine (CBF)	Berlin
Germany	Dominikus-Krankenhaus	Berlin
Germany	Humboldt-Klinikum - Vivantes - Netzwerk für Gesundheit GmbH	Berlin
Germany	Klinikum im Friedrichshain - Vivantes - Netzwerk für Gesundheit GmbH	Berlin
Germany	Paul Gerhard Diakonie - Evangelisches Krankenhaus Hubertus	Berlin
Germany	Paul Gerhard Diakonie - Evangelisches Waldkrankenhaus Spandau	Berlin
Germany	Paul Gerhard Diakonie - Martin-Luther-Krankenhaus	Berlin
Germany	Praxis Landgraf	Berlin
Germany	Sankt Jospeph Krankenhaus	Berlin
Germany	Unfallkrankenhaus Berlin	Berlin
Germany	Universitätsklinikum Mannheim GmbH	Berlin
Germany	Wenckebach-Klinikum - Vivantes - Netzwerk für Gesundheit GmbH	Berlin
Germany	Carl-Thiem-Klinikum	Cottbus
Germany	Werner Forßmann-Krankenhaus	Eberswalde
Germany	Klinikum Frankfurt Oder GmbH	Frankfurt/Oder
Germany	Universitätsklinikum Hamburg-Eppendorf	Hamburg
Germany	Asklepios Klinikum Harburg	Harburg
Germany	Sana Kliniken Sommerfeld	Kremmen
Germany	Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Universität zu Lübeck	Lübeck
Germany	Klinikum der Universität München, LMU Campus Großhadern	München
Germany	Klinikum rechts der Isar - Technische Universität München	München
Germany	München Klinik Bogenhausen	München
Germany	Praxis Prof. Dr med. Ulrich Schwantes	Schwante	Brandenburg

Sponsors (1)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frailty	Frequency of frailty is measured by modified Fried criteria (category 1 +2 = pre-frail, category 3 -5 = frail)	Up to 1 year
Primary	Neuro-cognitive disorder (NCD)	Frequency of neuro-cognitive disorder (mild / major NCD)	Up to 1 year
Secondary	Incidence of delirium	Incidence of delirium, defined according to Diagnostic and Statistical Manual of Mental Disorders (DSM-V), Richmond Agitation Scale (RASS), Nursing Delirium Screening Scale (Nu-DESC), Confusion Assessment Method (CAM), Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), along with the delirium severity scores Confusion Assessment Method Severity-Score (CAM-S) in English, Intensive Care Delirium Screening Checklist (ICDSC), Delirium Rating Scale Revised 98 (DRS-R-98) in English and patient chart review. The assessment period is from the recovery room up to five postoperative days or until hospital discharge.	During the hospital stay, an expected average of 1 week
Secondary	Severity of delirium	Severity of delirium defined as a composite score based on: Confusion Assessment Method Severity-Score(CAM-S); Confusion Assessment Method (CAM), Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), Delirium Rating Scale Revised (DSR-R-98) in English, Intensive Care Delirium Screening Checklist (ICDSC) and Nursing Delirium Screening Scale (Nu-DESC) and patient chart review.	During the hospital stay, an expected average of 1 week
Secondary	Nursing Delirium Screening Scale (Nu-DESC)	Nursing Delirium Screening Scale (Nu-DESC) score of = 2 is indicative of delirium, range: 0-10 points, 10 = most severe.	During the hospital stay, an expected average of 1 week
Secondary	Confusion Assessment Method (CAM)	Confusion Assessment Method (CAM) score is indicative of delirium, if the items 1 and 2 and 3 or the items 1 and 2 and 4 are measured positively.	During the hospital stay, an expected average of 1 week
Secondary	Confusion Assessment Method for the Intensive Care Unit (CAM-ICU)	Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) score is indicative of delirium, if the items 1 and 2 and 3 or the items 1 and 2 and 4 are measured positively.	During the hospital stay, an expected average of 1 week
Secondary	Confusion Assessment Method Severity-Score (CAM-S Long Form) in English	The Confusion Assessment Method Severity-Score (CAM-S Long Form) is an 10-item delirium screening instrument (range: 0-19 points, 19 = most severe).	During the hospital stay, an expected average of 1 week
Secondary	Intensive Care Delirium Screening Checklist (ICDSC)	The ICDSC is an 8-item delirium screening instrument (range: 0-8 points). The score is indicative of delirium, if the item is > 3.	During the hospital stay, an expected average of 1 week
Secondary	Delirium Rating Scale Revised 98 in English (DRS-R-98)	The delirium rating scale revised 98 is a delirium screening instrument (range 0-46). The score is indicative of delirium, if the item is > 14.5.	During the hospital stay, an expected average of 1 week
Secondary	Delirium Severity Scale (CAM-ICU-7) in English	A 7-point rating scale (0-7) was derived from the CAM-ICU and RASS assessments 0-2: no delirium, 3-5: mild to moderate delirium, and 6-7: severe delirium.	During the hospital stay, an expected average of 1 week
Secondary	Number of Participants with Delirium as Determined by Chart Review	Delirium is identified chart-based.	During the hospital stay, an expected average of 1 week
Secondary	Delirium days	The duration of delirium is measured in days.	During the hospital stay, an expected average of 1 week
Secondary	COVID-19	SARS-CoV-2 infection	Up to 1 year
Secondary	Cardiovascular function 1	Cardiovascular function is measured by Transesophageal Echocardiography.	Up to 1 year
Secondary	Cardiovascular function 2	Cardiovascular function is measured by cardiovascular complications.	Up to 1 year
Secondary	Ethical aspects	Wishes of the patient about the intensity of therapy and therapy goals are measured with a questionnaire.	Up to 1 year
Secondary	Patient satisfaction	Patient satisfaction score is measured with a likert scale (0 - 10)	Up to 1 year
Secondary	Patient-related outcome measures (PROMS)	Different tools and questionnaires are combined to measure Patient-related outcome.	Up to 1 year
Secondary	Patient-related experience measures (PREMS)	Patient-reported experiences of health care are measured with a questionnaire.	Up to 1 year
Secondary	Incidence of dementia	incidence of dementia is measured by MOCA	Up to 1 year
Secondary	Incidence of cognitive impairment	incidence of cognitive impairment is measured by a validated score.	Up to 1 year
Secondary	Findings of Memory consultation	During memory consultation cognitive diagnostic findings are measured.	Up to 1 year
Secondary	Stress	Stress is measured by Perceived Stress Questionnaire (PSQ20), which ranges from 20-80 points	Up to 1 year
Secondary	Anxiety 1	Anxiety is measured by Generalized Anxiety Disorder 7, points range from 0-21	Up to 1 year
Secondary	Anxiety 2	Anxiety 2 is measured by Faces Anxiety Scale, a valid single-item for self-report measure of state	Up to 1 year
Secondary	Insomnia	Insomnia is measured by Insomnia Severity Index (ISI), which ranges from 0- 21 points	Up to 1 year
Secondary	Neuroimaging	Routine neuroimaging results were planned to be documented in the hospital including all techniques to image the nervous system as ultrasound, magnetic resonance imaging, conventional radiography, computed tomography and positron emission tomography.	Up to 1 year
Secondary	Demand of health services	The need of treatment for curing an illness.	Up to 1 year
Secondary	Adverse events	Adverse events are measured in all participants, who receive study measurements	Up to 1 year
Secondary	Nutritional Status	Changes in the nutritional status after elective surgery	Up to 1 year
Secondary	Adherence to Mediterranean diet (MD)	Adherence to Mediterranean diet (MD) is measured with a German Medi-Score, could range from 0 to 9, with higher scores (6-9) indicating greater MD adherence.	Up to 1 year
Secondary	Sarcopenia	The composite outcome measure "Sarcopenia" is defined by the following three criteria: 1) low muscle strength (hand grip strength), 2) low muscle quantity (calf circumference and 3) low physical performance (gait speed). Criterion (1) identifies probable sarcopenia, additional documentation of criterion (2) confirms sarcopenia diagnosis, and if all criteria (1), (2) and (3) are met, sarcopenia is considered severe.	Up to 1 year
Secondary	Calf circumference	Calf circumference is measured in a standardized position and documented in centimeter.	Up to 1 year
Secondary	Arm circumference	Arm circumference is measured in a standardized position and documented in centimeter.	Up to 1 year
Secondary	Dental status	(number of teeth, Oral Health Assessment Tool (OHAT), Geriatric Oral Health Assessment Index (GO-HAI), questions regarding prothesis, dentist visits and dental care)	Up to 1 year
Secondary	Quality of life	Quality of life is measured by Care Related Quality of Life (CarerQoL)	Up to 1 year
Secondary	Postoperative complications	Complications are measured according to the Clavien-Dindo classification	Up to 30 days
Secondary	Psychometric properties of the Meta Memory questionnaire	Psychometric properties of the Meta Memory questionnaire are measured twice before surgery.	During the hospital stay, at the beginning of the investigation, an average of two hours.
Secondary	Number of participants with changes in laboratory values 1	Routine laboratory results were planned to be documented in the hospital including hemoglobin, lymphocytes, total neutrophils, platelet count and white blood cell (WBC) count from blood samples.	Up to 1 year
Secondary	Number of participants with changes in laboratory values 2	Routine laboratory results were planned to be documented from the general practitioner including hemoglobin, lymphocytes, total neutrophils, platelet count and white blood cell (WBC) count from blood samples.	Up to 1 year
Secondary	APOE polymorphisms	APOE polymorphisms are measured from whole blood once during hospital stay, an expected average of one week.	Up to 1 year
Secondary	Total interleukin-8	Total interleukin-8 is measured from whole blood	Up to 1 year
Secondary	Cholinesterases 1	Acetylcholinesterase and Butyrylcholinesterase are measured from liquor	Up to 1 year
Secondary	Cholinesterases 2	Acetylcholinesterase and Butyrylcholinesterase are measured from whole blood	Up to 1 year
Secondary	Intracellular pH	Intracellular pH is measured from whole blood.	Up to 1 year
Secondary	Autophagy of platelets	Autophagy of platelets is measured from whole blood.	Up to 1 year
Secondary	Peripheral Blood Mononuclear Cell	Peripheral Blood Mononuclear Cell are measured from whole blood.	Up to 1 year
Secondary	Multiplex gene expression analyzes (neuroinflammation and micro RNA panels)	Multiplex gene expression analyzes (neuroinflammation and micro RNA panels) are measured from whole blood	Up to 1 year
Secondary	Autoantibodies	Autoantibodies against beta2-adrenergic receptor, muscarinic acetylcholine receptor (M3 / M4), serotonin receptor, dopamine receptor are measured from serum	Up to 1 year
Secondary	Trypotophan metabolites and short-chain fatty acids	Trypotophan metabolites and short-chain fatty acids are measured from serum with metabolomic analysis	Up to 1 year
Secondary	Biomarker panel	Biomarker are measured from serum by metabolomic analyses to characterize the frailty complex.	Up to 1 year
Secondary	Cytokines	Cytokines (IFN-? IL-1ß IL-4 IL-6 IL-10 IL-17A IL-17E IL-17F IL-21 IL-23 TGF-ß1) are measured from plasma	Up to 1 year
Secondary	Chemokines	Chemokines (CCL2 (MCP-1) CCL3 CCL4 CCL5 (RAN-TES) CCL11 (Eotaxin) CCL19 CCL20 CXCL1 CXCL8 (IL-8) CXCL10 (IP-10) CXCL12 (SDF1A) are measured from plasma	Up to 1 year
Secondary	Markers immune-brain axis and gut-brain axis	Markers immune-brain axis and gut-brain axis (zonulin, endothelial cell-specific molecule 1, S100A6, S100A8, S100A9, S100P, S100beta, Interleu-kin-16, CD162, BDNF, CD272, p-selectin, be-ta2microglobulin , Haptoglobin, cathelicidin, NCAM-1, BTLA and CXCR5) are measured from plasma	Up to 1 year
Secondary	Protein panel	Proteins are measured from plasma by proteome analysis.	Up to 1 year
Secondary	Microbiome 1	Analyzes of bacteria-specific 16S DNA from different biomaterial.	Up to 1 year
Secondary	Microbiome 2	Analyzes of sequences of known microorganisms from different biomaterial.	Up to 1 year
Secondary	Serum albumin	Serum albumin is measured from whole blood	Up to 1 year
Secondary	HbA1c	HbA1c is measured from whole blood	Up to 1 year
Secondary	Vitamin D (cholecalciferol)	Vitamin D is measured from whole blood	Up to 1 year
Secondary	Dementia markers	Dementia markers: beta amyloid 1-40, beta-amyloid 1-42, beta-amyloid ratio (42/40 * 10), phospho-TAU, protein 14-3-3, PRPSc, TAU (total tau) are measured from liquor	Up to 1 year
Secondary	Analysis of microbiome	Microbial diversity is measured from blood, urine and feces (e.g. Shannon index)	Up to 1 year
Secondary	Analysis of urine	Relative frequency of metabolites is measured in urine	Up to 1 year
Secondary	Biobanks samples	Secondary use of the biological samples in particular for research purposes	Up to 1 year
Secondary	Hip Osteoarthritis Outcome	Hip Osteoarthritis Outcome is measured from Hip disability and Osteoarthritis Outcome Score (HOOS) in orthopedic patients from PG cohort	Up to 1 year
Secondary	Knee Osteoarthritis Outcome	Knee Osteoarthritis Outcome is measured from Knee injury and Osteoarthritis Outcome (KOOS) in orthopedic patients from PG cohort	Up to 1 year
Secondary	Gait analysis 1	Temporal (e.g.: total activity duration, stance time) parameters are measured in orthopedic patients from PG cohort.	Up to 1 year
Secondary	Gait analysis 2	Kinetic parameters (e.g.: vertical plantar loading, loading symmetry) are measured in orthopedic patients from PG cohort.	Up to 1 year
Secondary	Range of Motion of the hip/knee	Range of Motion of the hip/knee is measured during orthopedic investigation of PG cohort patients	Up to 1 year
Secondary	Hip abduction force (for total hip arthroplasty patients)	Hip abduction force is measured during orthopedic investigation of PG cohort patients	Up to 1 year
Secondary	Knee extension and flexion force measurement (for total knee arthroplasty patients)	Knee extension and flexion force measurement is measured during orthopedic investigation of PG cohort patients	Up to 1 year
Secondary	Clinical investigation	Clinical investigation is measured by a neurosurgical method in patients from PG and NFC cohorts who undergo elective spine surgery and in control patients from NO cohort	Up to 1 year
Secondary	Oswestry disability index (ODI)	ODI is measured in patients from PG and NFC cohorts who undergo elective spine surgery and in control patients from NO cohort.	Up to 1 year
Secondary	Back pain	Low Back pain is measured by the Roland Morris Low Back pain and disability questionnaire in patients (PG, NFC, NO cohorts) with lumbal spine problems.	Up to 1 year
Secondary	Leg pain	Leg pain is measured by 100mm visual analog scale in patients (PG, NFC, NO cohorts) with lumbal spine problems.	Up to 1 year
Secondary	Sciatica Bothersomeness Index	To establish values for paresthesia, weakness and leg pain the Sciatica Bothersomeness Index is measured n patients (PG, NFC, NO cohorts) with lumbal spine problems.	Up to 1 year
Secondary	Disabilities of the Arm, Shoulder and Hand Questionnaire (DASH)	To measure Disabilities of the Arm, Shoulder and Hand the DASH questionnaire is used in patient (PG, NFC, NO cohort) in patients with cervical spine problems	Up to 1 year
Secondary	Modified Japanese orthopaedic association scale	The modified Japanese Orthopaedic Association scale is used to establish criteria for mild, moderate and severe impairment in patients with degenerative cervical myelopathy in patients (PG, NFC, NO cohorts) with cervical spine problems	Up to 1 year
Secondary	ASIA Impairment Scale (AIS)	ASIA Impairment Scale is used to measure for patients with spinal myelopathies or spinal cord injuries in patients from PG and NFC cohorts who undergo elective spine surgery and in control patients from NO cohort	Up to 1 year
Secondary	Skill management	Multiprofessional skill management is evaluated in all participating occupations of the GB cohort in qualitative interviews.	Up to 1 year
Secondary	Acceptance of participatory decision-making	Acceptance of participatory decision-making before and after participating in an SDM conference.	Up to 1 year
Secondary	Depth of anesthesia	Depth of anesthesia is measured by brainwaves in different patient states which range from awake, sedated, unresponsive, surgically anesthetized to deeply anesthetized.	During surgery, an expected average of 2 hours
Secondary	Electroencephalography spectral analysis	Electroencephalography spectral analysis is measured by brainwaves preoperatively.	During the hospital stay, at the beginning of the investigation, an average of one hour.
Secondary	Electroencephalography band power	Electroencephalography band power is measured postoperatively by an electroencephalography monitor at postoperative day 3 in all patients and in patients with delirium until 48 hours without positive delirium screening	During the hospital stay, an expected average of 1 week
Secondary	Effect of analgesics	Pain is evaluated with the Dolosys Paintracker. The Paintracker is a handy monitoring device to determine the analgesia needed for patients based on the pain reflex technique.	During the hospital stay, an expected average of 1 week