Clinical trial NCT02396277: Structural and Functional Nerve Changes Following Immobilisation After Distal Radius Fracture - a Pilot Study (NRP)
Official title: Structural and Functional Nerve Changes Following Immobilisation After Distal Radius Fracture - a Pilot Study (NRP)
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Colles' Fracture
Distal Radius Fracture
Lead sponsor: University of Tromso
Sponsor class: OTHER
First posted: 2015-03-24
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients referred to the Emergency Clinic at The University Hospital in North Norway Tromso day time

Brief summary: Immobilization after radius fracture seems to increase the risk of developing a Complex regional pain syndrome (CRPS), a condition associated with pain, increased skin sensitivity and reduced epidermal nerve density.

The purpose of the study is to determine whether 5-week immobilisation leads to functional and structural sensory changes, and whether the changes are associated with persistent pain. The investigators plan an explorative, pilot study on six consenting patients immobilised after a distal radius fracture.

The baseline measurements will be recorded at the day of or the day after trauma: Demographics, psychological and physical comorbidity, pain characteristics and intensity, hand function, health related quality of life (HRQOL), quantitative sensory testing will be recorded while skin biopsies are analyzed for epidermal nerve fiber density. Following variables such as pain characteristics and intensity, hand function, health related quality of life, quantitative sensory testing and skin biopsies will be reassessed when the cast is removed and two months later.

Detailed description: Distal radius fracture is a prevalent injury, affecting 15.000 cases in Norway every year. About 5% of these patients suffer from longlasting pain and some develop a serious and chronic CRPS. Patients subjected to hand surgery frequently report pain one month after cast removal, and further examinations have revealed vascular and trophic changes, and increased sensitivity to pressure and cold as well as elevated skin levels of proinflammatory mediators.

Long term immobilization seems to increase the risk of developing CRPS symptoms. In a Danish study healthy volunteers demonstrated increased hyperalgesia to cold and mechanical stimuli even after 4-week immobilization which may indicate an early change in the nerve function.

In CRPS patients skin biopsies have demonstrated reduced epidermal nerve fiber density, but such data are lacking after radius fracture and during early stage of CRPS.

The purpose of this explorative, observational, pilot study is to investigate whether radius fracture followed by 5-week of immobilization, leads to functional and structural changes of the sensory system which are reversed after remobilization and whether the sensory changes are associated with persistent pain.

Our hypotheses are: 1) Patients with an immobilised arm following a radius fracture develops a) early cutaneous hypersensitivity (hyperalgesia and allodynia) for mechanical og thermal stimuli and b) reduced epidermal nerve fiber density.

2) The changes of the sensory system are reversed after 2-month remobilization. 3) The functional and structural changes are correlated with patient reported outcome measures (PROM) such as disability of arm, shoulder and hand (DASH), with pain intensity (NRS), duration of the pain and HRQOL .

Eligible patients will be included throughout 2015, and results will be analyzed within December 2015.

Measurements:

Self reported: Demographics (age, gender, civil state, education, working status, social security benefits) and clinical data of comorbidity, pain characteristics (DN4) and intensity (NRS), blood pressure, smoking /other kind of nicotine use, pain medication, and assessment scales for mental distress (HSCL 25), pain catastrophizing (PCS), hand function (DASH), and HRQOL (EQ5D).

Examinations: Quantitative sensory testing (tactile and thermal stimuli) and skin biopsies are carried out 10 cm proximal to fracture line on the dorsum of the affected arm. Measurements for predictor analyses will only be performed at baseline while outcome measurements will be performed prior to and just after removal of the cast as well as two months later.

Statistical analyses:

Regression analyses will be performed to identify other predictors for the changes in sensory nervous system including blood pressure, smoking /other kind of nicotine use, medication, age, gender, and comorbidity. Longitudinal analyses of numerical outcome (ANOVA repeated measurement) will be carried out for outcome measurements such as pain intensity,hand function, HRQOL, sensory thresholds and epidermal nerve fiber density.

Eligibility criteria: Inclusion Criteria:

* Consent competence
* Acute stable distal radius fracture (less than 48 hours)
* Allocated to conservative treatment with 5-week immobilization

Exclusion Criteria:

* Comorbidity which may prevent completion of the study
* Serious and progressive disease
* Chronic shoulder disease with limited ROM and function.
* Sign peripheral nerve injury in the upper extremities
* Polyneuropathy
* Demyelination disease
* Diabetes mellitus
* Anticoagulants including acetyl salicylic acid (ASA)
* Allergy to local anesthetics

Primary outcomes:
measure: Changes from baseline in nerve fiber density at five weeks
timeFrame: From baseline to five weeks after injury
measure: Changes from baseline in sensitivity to thermal and tactile stimuli at five weeks
timeFrame: From baseline to five weeks after injury
Secondary outcomes:
measure: Changes from five weeks in nerve fiber density at 13 weeks
timeFrame: From five weeks to 13 weeks after injury
measure: Changes from five weeks in sensitivity to thermal and tactile stimuli at 13 weeks
timeFrame: From five to 13 weeks after injury
measure: Correlation between changes in pain intensity and changes in nerve fiber density
timeFrame: From baseline to 13 weeks
measure: Correlation between changes in pain intensity and changes in sensitivity to thermal and tactile stimuli
timeFrame: From baseline to 13 weeks
measure: Changes from baseline (preinjury) in disability of arm, shoulder and hand are correlated with changes in pain intensity at five and 13 weeks
timeFrame: From baseline to 13 weeks
measure: Changes from baseline (preinjury) HRQOL are correlated with changes in pain intensity at five and 13 weeks
timeFrame: From baseline to 13 weeks
Other outcomes:
Locations:
city: Tromso
country: Norway
facility: University Hospital of North Norway
Study officials:
affiliation: University of Tromso
name: Gunnvald Kvarstein, PhD
role: STUDY_CHAIR
References: