- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT07642726
Change in Cognition and Frailty After Shunt Surgery in Idiopathic Normal Pressure Hydrocephalus (iNPH)
Studieoversigt
Status
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
Idiopathic normal pressure hydrocephalus (iNPH) is characterized by one or more of the symptoms gait disturbance, cognitive decline and urinary incontinence. The pathophysiology is not fully understood, but disturbed cerebrospinal fluid (CSF) circulation is considered one of the contributing factors. The CSF disturbance can be treated by shunt surgery with significant improvement in gait velocity and balance, whereas improvements in cognitive function are more uncertain.
Frailty is a consequence of cumulative decline in many physiological systems during a lifetime and implies an increased vulnerability to poor resolution of homoeostasis after a stressor event. Frailty is emerging as an important risk factor for mortality and postoperative complications but has to a limited degree been studied in iNPH.
We have previously, in a cross-sectional design, described cognitive profile and frailty status in patients with iNPH accepted for shunt surgery at Oslo University Hospital. The aims of this longitudinal follow-up of the same patient cohort are twofold:
- to describe changes in cognitive profile and frailty from pre shunt to one year after the shunt surgery, and
- to identify clinical predictors of an improvement in terms of cognition and frailty during the same period.
The patient sample consists of 276 patients that were accepted for shunt surgery at Oslo University Hospital in the period from September 2018 to December 2023. Their mean age was 73.1 years (range 52-85), 61% were men, and their mean length of education was 12.5 years. For the cognitive tests, we utilised z-scores (number of standard deviations (SD) from the age and education adjusted mean in a normative dataset).
For frailty, we used a 35 items Frailty Index (FI). Most of the items (frailty indicators) are scored 0 (not present) or 1 (present), while some of them have a graded score. The index is the sum score divided by the number of items, varying from 0.0 (no frailty) to 1.0 (extreme frailty). We used the same approach for assessment of the degree of frailty within each frailty domain. Cognitive decline is considered as one component of frailty. Accordingly, the Mini Mental State Examination (MMSE) is part of the FI and has a graded score. MMSE sum score <21 gives a score of 1 at this particular FI item, an MMSE score of 21-23 gives an item score of 0.7, an MMSE score of 24-26 gives an item score of 0.3, whereas an MMSE score of 27-30 does not contribute to the FI. MMSE is a screening test covering several cognitive domains. We will use MMSE to evaluate the cognitive dimension of frailty as described here, whereas more specific cognitive tests are utilised to assess failure in particular cognitive domains.
Preoperatively, the mean FI score was 0.23, and the most common frailty markers were in the domains of physical function and instrumental activities of daily living (iADL). On the group level, the iNPH patients were impaired on all cognitive domains preoperatively, but compared to patients with Alzheimer's disease, they had relatively better-preserved memory and more severe impairments in phonemic fluency.
220 (80%) patients were assessed one year postoperatively. The same cognitive tests and frailty assessments were carried out, making it possible to calculate simple change scores as score(postop) - score(preop). We will compare baseline characteristics of patients lost to follow-up descriptively with those followed, to assess potential attrition bias.
A detailed Statistical Analysis Plan (SAP) describes the planned analytical approach.
Undersøgelsestype
Tilmelding (Faktiske)
Kontakter og lokationer
Studiesteder
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Oslo, Norge
- Department of Geriatric Medicine, Oslo University Hospital
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
- Barn
- Voksen
- Ældre voksen
Tager imod sunde frivillige
Prøveudtagningsmetode
Studiebefolkning
Beskrivelse
Inclusion Criteria:
• Diagnosed with iNPH and accepted for shunt surgery according to the American-European guidelines at Department of Neurosurgery, Oslo University Hospital, Rikshospitalet.
Exclusion Criteria:
- Non-native speakers of Norwegian
- Patients who had completed ≤ 3 cognitive tests
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
Kohorter og interventioner
Gruppe / kohorte |
Intervention / Behandling |
|---|---|
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Patients with idiopathic normal pressure hydrocephalus accepted for shunt surgery
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Patients are already accepted for shunt surgery.
We will describe changes in cognitve profile and frailty from pre shunt to one year after to identify clinical predictors for shunt response.
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Change in Trail Making Test A (TMT A) from preoperative to postoperative in patients with idiopathic normal pressure hydrocephalus (iNPH).
Tidsramme: 12 month
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TMT A is a cognitive test assessing attention and psychomotor speed and z-scores are calculated using age and educational adjusted norms.
The lowest/highest possible z-score is - 3/+ 3 and indicates - 3/+ 3 SD from the mean.
Higher z-score reflects better performance.
We have defined a Minimum Clinically Important Difference (MCID) as an increase in the z-score (number of standard deviations (SD)) from the age and education adjusted mean in a normative dataset of 0.5 or more for TMT A.
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12 month
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Change in Frailty Index (FI) from preoperative to postoperative in patients with idiopathic normal pressure hydrocephalus (iNPH).
Tidsramme: 12 months
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For frailty, a 35 items FI was used.
Most of the items (frailty indicators) are scored 0 (not present) or 1 (present), while some of them have a graded score.
The index is the sum score divided by the numbers of items, varying from 0.0 (no frailty) to 1.0 (extreme frailty).
We have defined a Minimum Clinically Important Difference (MCID) as a decrease in the FI of 0.05 (5 %) or more.
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12 months
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Other measures of cognition and frailty
Tidsramme: 12 months
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Cognitive variables: For assessing memory, delayed word recall (z score from either Consortium to Establish a Registry for Alzheimer's disease (CERAD) ten words memory test or the Rey Auditory Learning Test were used. The lowest/highest possible z-score is - 3/+ 3 and indicates - 3/+ 3 SD from the mean. Higher z-score reflects better performance. MCID: Z-score difference 0.5. |
12 months
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Other measures of cognition and frailty
Tidsramme: 12 months
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Figure Construction Test from CERAD is a cognitive test assessing visuoconstructive abilities.
The lowest/highest possible z-score is - 3/+ 3 and indicates - 3/+ 3 SD from the mean.
Higher z-score reflects better performance.
MCID: Z-score difference 0.5.
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12 months
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Other measures of cognition and frailty
Tidsramme: 12 months
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Trail Making Test B is a cognitive test assessing attention, psychomotor speed and executive function.
The lowest/highest possible z-score is - 3/+ 3 and indicates - 3/+ 3 SD from the mean.
Higher z-score reflects better performance.
MCID: Z-score difference 0.5.
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12 months
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Other measures of cognition and frailty
Tidsramme: 12 months
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The Phonemic Fluency Test is a cognitive test assessing language abilities and executive function.
The lowest/highest possible z-score is - 3/+ 3 and indicates - 3/+ 3 SD from the mean.
Higher z-score reflects better performance.
MCID: Z-score difference 0.5.
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12 months
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Other measures of cognition and frailty
Tidsramme: 12 months
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Mini Mental State Examination (MMSE-NR3) is a cognitive screening test from 0 - 30 covering several cognitive domains.
Higher score indicates better function.
MMSE is part of the FI and has a graded score.
MMSE sum score <21 gives a score of 1 at this particular FI item, an MMSE score of 21-23 gives an item score of 0.7, an MMSE score of 24-26 gives an item score of 0.3, whereas an MMSE score of 27-30 does not contribute to the FI.
MCID: 2 points.
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12 months
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Other measures of cognition and frailty
Tidsramme: 12 months
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Personal activities in daily living (pADL) are subscales of the FI and are scored from 0-7, higher score indicates more need for help in daily living.
An improvement is set to at least 5 % for subscale as a limit for MCID.
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12 months
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Other measures of cognition and frailty
Tidsramme: 12 months
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Instrumental activities in daily living (iADL) are subscales of the FI and are scored from 0-7, higher score indicates more need for help in daily living.
An improvement is set to at least 5 % for subscale as a limit for MCID.
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12 months
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Other measures of cognition and frailty
Tidsramme: 12 months
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Gait speed (m/s) is measured from 10 m walk and 0.1 m/s or more is accepted as clinically meaningful.
MCID is set to 0.1 m/s.
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12 months
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Andre resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Responder analysis
Tidsramme: 12 months
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Based on the MCID limits for each outcome, we will define a responder for each outcome as a patient improving that much or more from the preoperative to the one-year postoperative assessment and will calculate the percentage of responders for each of the outcomes. We will then analyse predictors for shunt response on each of the ten outcome variables. Candidate variables in the prediction models are: 1. Age. 2. Sex. 3. MMSE-NR3 score. 4. Gait speed. 5. FI score. 6. Difference in z-score between phonemic fluency and delayed recall at baseline. 7. Cluster affiliation (based on a previously published cluster analysis. The analytic strategy is described in detail in the Statistical Analysis Plan (SAP) that is uploaded as a separate document. |
12 months
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Samarbejdspartnere og efterforskere
Sponsor
Publikationer og nyttige links
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Faktiske)
Studieafslutning (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
- Hjernesygdomme
- Sygdomme i centralnervesystemet
- Sygdomme i nervesystemet
- Psykiske lidelser
- Patologiske processer
- Neurokognitive lidelser
- Kognitionsforstyrrelser
- Patologiske tilstande, tegn og symptomer
- Tegn og symptomer
- Skrøbelighed
- Kognitiv dysfunktion
- Mobilitetsbegrænsning
- Demens
- Kirurgiske procedurer, operative
- Neurokirurgiske procedurer
- Anastomose, kirurgisk
- Cerebrospinalvæskeshunter
- Ventriculoperitoneal shunt
Andre undersøgelses-id-numre
- 10150 (formerly 2019/547)
- Funded by (Anden identifikator: Department of Geriatric Medicine Oslo University Hospital)
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
IPD-planbeskrivelse
IPD-delingsadgangskriterier
IPD-deling Understøttende informationstype
- STUDY_PROTOCOL
- SAP
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