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NCT Number: NCT04880824

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

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.

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Key information

Age range

70 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Praxis Prof. Dr med. Ulrich Schwantes, Schwante, Brandenburg, Germany

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About this study

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.)

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Prehabilitation- new form of care

Behavioral

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.

Primary outcomes

  1. Frailty

    Time frame: Up to 1 year

    Frequency of frailty is measured by modified Fried criteria (category 1 +2 = pre-frail, category 3 -5 = frail)

  2. Neuro-cognitive disorder (NCD)

    Time frame: Up to 1 year

    Frequency of neuro-cognitive disorder (mild / major NCD)

Secondary outcomes

  1. Incidence of delirium

    Time frame: During the hospital stay, an expected average of 1 week

    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.

  2. Severity of delirium

    Time frame: During the hospital stay, an expected average of 1 week

    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.

  3. Nursing Delirium Screening Scale (Nu-DESC)

    Time frame: During the hospital stay, an expected average of 1 week

    Nursing Delirium Screening Scale (Nu-DESC) score of ≥ 2 is indicative of delirium, range: 0-10 points, 10 = most severe.

  4. Confusion Assessment Method (CAM)

    Time frame: During the hospital stay, an expected average of 1 week

    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.

  5. Confusion Assessment Method for the Intensive Care Unit (CAM-ICU)

    Time frame: During the hospital stay, an expected average of 1 week

    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.

  6. Confusion Assessment Method Severity-Score (CAM-S Long Form) in English

    Time frame: During the hospital stay, an expected average of 1 week

    The Confusion Assessment Method Severity-Score (CAM-S Long Form) is an 10-item delirium screening instrument (range: 0-19 points, 19 = most severe).

  7. Intensive Care Delirium Screening Checklist (ICDSC)

    Time frame: During the hospital stay, an expected average of 1 week

    The ICDSC is an 8-item delirium screening instrument (range: 0-8 points). The score is indicative of delirium, if the item is > 3.

  8. Delirium Rating Scale Revised 98 in English (DRS-R-98)

    Time frame: During the hospital stay, an expected average of 1 week

    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.

  9. Delirium Severity Scale (CAM-ICU-7) in English

    Time frame: During the hospital stay, an expected average of 1 week

    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.

  10. Number of Participants with Delirium as Determined by Chart Review

    Time frame: During the hospital stay, an expected average of 1 week

    Delirium is identified chart-based.

  11. Delirium days

    Time frame: During the hospital stay, an expected average of 1 week

    The duration of delirium is measured in days.

  12. COVID-19

    Time frame: Up to 1 year

    SARS-CoV-2 infection

  13. Cardiovascular function 1

    Time frame: Up to 1 year

    Cardiovascular function is measured by Transesophageal Echocardiography.

  14. Cardiovascular function 2

    Time frame: Up to 1 year

    Cardiovascular function is measured by cardiovascular complications.

  15. Ethical aspects

    Time frame: Up to 1 year

    Wishes of the patient about the intensity of therapy and therapy goals are measured with a questionnaire.

  16. Patient satisfaction

    Time frame: Up to 1 year

    Patient satisfaction score is measured with a likert scale (0 - 10)

  17. Patient-related outcome measures (PROMS)

    Time frame: Up to 1 year

    Different tools and questionnaires are combined to measure Patient-related outcome.

  18. Patient-related experience measures (PREMS)

    Time frame: Up to 1 year

    Patient-reported experiences of health care are measured with a questionnaire.

  19. Incidence of dementia

    Time frame: Up to 1 year

    incidence of dementia is measured by MOCA

  20. Incidence of cognitive impairment

    Time frame: Up to 1 year

    incidence of cognitive impairment is measured by a validated score.

  21. Findings of Memory consultation

    Time frame: Up to 1 year

    During memory consultation cognitive diagnostic findings are measured.

  22. Stress

    Time frame: Up to 1 year

    Stress is measured by Perceived Stress Questionnaire (PSQ20), which ranges from 20-80 points

  23. Anxiety 1

    Time frame: Up to 1 year

    Anxiety is measured by Generalized Anxiety Disorder 7, points range from 0-21

  24. Anxiety 2

    Time frame: Up to 1 year

    Anxiety 2 is measured by Faces Anxiety Scale, a valid single-item for self-report measure of state

  25. Insomnia

    Time frame: Up to 1 year

    Insomnia is measured by Insomnia Severity Index (ISI), which ranges from 0- 21 points

  26. Neuroimaging

    Time frame: Up to 1 year

    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.

  27. Demand of health services

    Time frame: Up to 1 year

    The need of treatment for curing an illness.

  28. Adverse events

    Time frame: Up to 1 year

    Adverse events are measured in all participants, who receive study measurements

  29. Nutritional Status

    Time frame: Up to 1 year

    Changes in the nutritional status after elective surgery

  30. Adherence to Mediterranean diet (MD)

    Time frame: Up to 1 year

    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.

  31. Sarcopenia

    Time frame: Up to 1 year

    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.

  32. Calf circumference

    Time frame: Up to 1 year

    Calf circumference is measured in a standardized position and documented in centimeter.

  33. Arm circumference

    Time frame: Up to 1 year

    Arm circumference is measured in a standardized position and documented in centimeter.

  34. Dental status

    Time frame: Up to 1 year

    (number of teeth, Oral Health Assessment Tool (OHAT), Geriatric Oral Health Assessment Index (GO-HAI), questions regarding prothesis, dentist visits and dental care)

  35. Quality of life

    Time frame: Up to 1 year

    Quality of life is measured by Care Related Quality of Life (CarerQoL)

  36. Postoperative complications

    Time frame: Up to 30 days

    Complications are measured according to the Clavien-Dindo classification

  37. Psychometric properties of the Meta Memory questionnaire

    Time frame: During the hospital stay, at the beginning of the investigation, an average of two hours.

    Psychometric properties of the Meta Memory questionnaire are measured twice before surgery.

  38. Number of participants with changes in laboratory values 1

    Time frame: Up to 1 year

    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.

  39. Number of participants with changes in laboratory values 2

    Time frame: Up to 1 year

    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.

  40. APOE polymorphisms

    Time frame: Up to 1 year

    APOE polymorphisms are measured from whole blood once during hospital stay, an expected average of one week.

  41. Total interleukin-8

    Time frame: Up to 1 year

    Total interleukin-8 is measured from whole blood

  42. Cholinesterases 1

    Time frame: Up to 1 year

    Acetylcholinesterase and Butyrylcholinesterase are measured from liquor

  43. Cholinesterases 2

    Time frame: Up to 1 year

    Acetylcholinesterase and Butyrylcholinesterase are measured from whole blood

  44. Intracellular pH

    Time frame: Up to 1 year

    Intracellular pH is measured from whole blood.

  45. Autophagy of platelets

    Time frame: Up to 1 year

    Autophagy of platelets is measured from whole blood.

  46. Peripheral Blood Mononuclear Cell

    Time frame: Up to 1 year

    Peripheral Blood Mononuclear Cell are measured from whole blood.

  47. Multiplex gene expression analyzes (neuroinflammation and micro RNA panels)

    Time frame: Up to 1 year

    Multiplex gene expression analyzes (neuroinflammation and micro RNA panels) are measured from whole blood

  48. Autoantibodies

    Time frame: Up to 1 year

    Autoantibodies against beta2-adrenergic receptor, muscarinic acetylcholine receptor (M3 / M4), serotonin receptor, dopamine receptor are measured from serum

  49. Trypotophan metabolites and short-chain fatty acids

    Time frame: Up to 1 year

    Trypotophan metabolites and short-chain fatty acids are measured from serum with metabolomic analysis

  50. Biomarker panel

    Time frame: Up to 1 year

    Biomarker are measured from serum by metabolomic analyses to characterize the frailty complex.

  51. Cytokines

    Time frame: Up to 1 year

    Cytokines (IFN-Ɣ IL-1β IL-4 IL-6 IL-10 IL-17A IL-17E IL-17F IL-21 IL-23 TGF-β1) are measured from plasma

  52. Chemokines

    Time frame: Up to 1 year

    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

  53. Markers immune-brain axis and gut-brain axis

    Time frame: Up to 1 year

    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

  54. Protein panel

    Time frame: Up to 1 year

    Proteins are measured from plasma by proteome analysis.

  55. Microbiome 1

    Time frame: Up to 1 year

    Analyzes of bacteria-specific 16S DNA from different biomaterial.

  56. Microbiome 2

    Time frame: Up to 1 year

    Analyzes of sequences of known microorganisms from different biomaterial.

  57. Serum albumin

    Time frame: Up to 1 year

    Serum albumin is measured from whole blood

  58. HbA1c

    Time frame: Up to 1 year

    HbA1c is measured from whole blood

  59. Vitamin D (cholecalciferol)

    Time frame: Up to 1 year

    Vitamin D is measured from whole blood

  60. Dementia markers

    Time frame: Up to 1 year

    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

  61. Analysis of microbiome

    Time frame: Up to 1 year

    Microbial diversity is measured from blood, urine and feces (e.g. Shannon index)

  62. Analysis of urine

    Time frame: Up to 1 year

    Relative frequency of metabolites is measured in urine

  63. Biobanks samples

    Time frame: Up to 1 year

    Secondary use of the biological samples in particular for research purposes

  64. Hip Osteoarthritis Outcome

    Time frame: Up to 1 year

    Hip Osteoarthritis Outcome is measured from Hip disability and Osteoarthritis Outcome Score (HOOS) in orthopedic patients from PG cohort

  65. Knee Osteoarthritis Outcome

    Time frame: Up to 1 year

    Knee Osteoarthritis Outcome is measured from Knee injury and Osteoarthritis Outcome (KOOS) in orthopedic patients from PG cohort

  66. Gait analysis 1

    Time frame: Up to 1 year

    Temporal (e.g.: total activity duration, stance time) parameters are measured in orthopedic patients from PG cohort.

  67. Gait analysis 2

    Time frame: Up to 1 year

    Kinetic parameters (e.g.: vertical plantar loading, loading symmetry) are measured in orthopedic patients from PG cohort.

  68. Range of Motion of the hip/knee

    Time frame: Up to 1 year

    Range of Motion of the hip/knee is measured during orthopedic investigation of PG cohort patients

  69. Hip abduction force (for total hip arthroplasty patients)

    Time frame: Up to 1 year

    Hip abduction force is measured during orthopedic investigation of PG cohort patients

  70. Knee extension and flexion force measurement (for total knee arthroplasty patients)

    Time frame: Up to 1 year

    Knee extension and flexion force measurement is measured during orthopedic investigation of PG cohort patients

  71. Clinical investigation

    Time frame: Up to 1 year

    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

  72. Oswestry disability index (ODI)

    Time frame: Up to 1 year

    ODI is measured in patients from PG and NFC cohorts who undergo elective spine surgery and in control patients from NO cohort.

  73. Back pain

    Time frame: Up to 1 year

    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.

  74. Leg pain

    Time frame: Up to 1 year

    Leg pain is measured by 100mm visual analog scale in patients (PG, NFC, NO cohorts) with lumbal spine problems.

  75. Sciatica Bothersomeness Index

    Time frame: Up to 1 year

    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.

  76. Disabilities of the Arm, Shoulder and Hand Questionnaire (DASH)

    Time frame: Up to 1 year

    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

  77. Modified Japanese orthopaedic association scale

    Time frame: Up to 1 year

    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

  78. ASIA Impairment Scale (AIS)

    Time frame: Up to 1 year

    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

  79. Skill management

    Time frame: Up to 1 year

    Multiprofessional skill management is evaluated in all participating occupations of the GB cohort in qualitative interviews.

  80. Acceptance of participatory decision-making

    Time frame: Up to 1 year

    Acceptance of participatory decision-making before and after participating in an SDM conference.

  81. Depth of anesthesia

    Time frame: During surgery, an expected average of 2 hours

    Depth of anesthesia is measured by brainwaves in different patient states which range from awake, sedated, unresponsive, surgically anesthetized to deeply anesthetized.

  82. Electroencephalography spectral analysis

    Time frame: During the hospital stay, at the beginning of the investigation, an average of one hour.

    Electroencephalography spectral analysis is measured by brainwaves preoperatively.

  83. Electroencephalography band power

    Time frame: During the hospital stay, an expected average of 1 week

    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

  84. Effect of analgesics

    Time frame: During the hospital stay, an expected average of 1 week

    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.

Sponsors and collaborators

Lead sponsor

Charite University, Berlin, Germany

Other

Registry information

Official study 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)

Important dates

Study start
2021
Primary completion
2025
Study completion
2025
First posted
May 11, 2021
Registry last updated
Aug 26, 2025

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