Treatment for Ulnar Neuropathy at the Elbow - a Randomized Control Trial
Phase: NA
Conditions: Peripheral Nervous System Diseases, Nerve Compression Syndromes, Cubital Tunnel Syndrome
Sponsor: University Medical Centre Ljubljana

STUDY PROTOCOL with STATISTICS 
Treatment for Ulnar Neuropathy at the Elbow - a Randomized Control Trial 
NCT Number: NCT03651609  
January 3, 2019 
 
Patients 
From January 2019, consecutive patients with suspected UNE will be prospectively recruited 
in a single referral centre (Institute of Clinical Neurophysiology, University Medical Center 
Ljubljana, Slovenia). Inclusion criteria will be: (1) sensory loss in the 5th ﬁnger; (2) weakness 
of 2nd and 5th finger abduction; and (3) UNE confirmed and precisely localized by short-
segment nerve conduction studies (NCSs) and US. Exclusion criteria will be: (1) previous 
elbow fracture or surgery; (2) sensory loss outside of the ulnar innervation area; (3) an ulnar 
nerve conduction block of > 20% in the elbow segment; (4) C8 radiculopathy, lower brachial 
plexopathy, or ulnar neuropathy at the wrist; (5) polyneuropathy or multiple mononeuropathy; 
(6) spinal cord anterior horn cell disorders (e.g., monomelic amyotrophy, amyotrophic lateral 
sclerosis).  
The trial protocol will conform to CONSORT guidelines. Written informed consent will be 
obtained from all patients before their inclusion into the study. The trial was approved by the 
National Ethics Committee of Slovenia (Nr. 0120-497/2018/5) and was registered on the 27th 
of August 2018 at ClinicalTrials.gov (NCT03651609). 
 
History and Clinical Neurologic Examination 
The ﬁrst examiner will collect demographic and clinical data using a standard questionnaire 
for assessment of UNE severity (UNEQ).1 The UNEQ considers the patient's numbness and 
tingling of the last two fingers, elbow pain, and changes in these symptoms with elbow 

position. It also evaluates hand weakness. Questionnaire items are graded as: 1 – absent, 2 – 
mild, 3 – moderate, 4 – severe, or 5 – very severe. The final UNEQ score is calculated as the 
mean of the nine items.1 Patients will also report whether UNE symptoms: 1 – improved, 2 – 
remained unchanged, or 3 – worsened. The ﬁrst examiner will also perform a focused 
neurological examination and graded: (1) muscle wasting of the first dorsal interosseous 
(FDI) and abductor digiti minimi (ADM) muscles (0 – absent, 1 – mild, 2 – moderate or 3 – 
severe); (2) muscle strength of FDI, ADM, and four indicator forearm muscles using the 
modified MRC scale;
2 and (3) light touch and pin-prick sensation on the tip of the 5th and 2nd 
finger, ulnar sides of the 4th finger, palm, and hand dorsum as well as the forearm (0 – 
normal, 1 – moderately reduced, 2 – severely reduced or 3 – absent). For statistical analyses, 
the modified MRC scale will be transformed as follows: MRC grade 0 = 0, 1 = 1, 2 = 2, 3 = 3, 
4– = 4, 4 = 5, 4+ = 6, and 5 = 7. Clinical UNE severity was graded: (1) Mild UNE – reduced 
sensation in the ulnar-innervated areas; (2) Moderate UNE – + ulnar hand muscle weakness, 
and (3) Severe UNE – + at least moderate ulnar hand muscle atrophy. 
 
Electrodiagnostic Examination (EDx) 
The second examiner (clinical neurophysiologist > 25 years) will also perform motor and 
sensory NCSs of the ulnar and median nerve in the affected arms using a standard EMG 
system (Nicolet Synergy, Natus Medical Incorporated, San Carlos, USA). Compound muscle 
action potentials (CMAPs) will be recorded from the ADM and abductor pollicis brevis 
(APB) muscles using disposable adhesive surface electrodes. With the elbow ﬂexed at 90º, the 
ulnar nerve will be stimulated at the wrist, ME, 2 and 4 cm distal (D2, D4), and 2 and 4 cm 
proximal (P2, P4) to ME (i.e., short-segment NCSs). The median nerve will be stimulated at 
the wrist and the elbow. Ulnar and median antidromic sensory nerve action potentials 

(SNAPs) will be recorded from the 5th and 2nd ﬁngers on stimulation 14 cm proximally at the 
wrist.  
Using short-segment NCSs, UNE will be diagnosed and localized to a 2-cm ulnar nerve 
segment with either motor nerve conduction velocity (MNCV) < 31 m/s (the lower reference 
limit) or a CMAP amplitude drop > 12% (the upper reference limit) (Fig. 1).3  
 
Ultrasonography (US) 
The third examiner (US technician >10 years) will measure the ulnar and median nerve CSAs 
in the affected arm using a standard US device (ProSound Alpha 7, Hitachi Aloka Medical, 
Ltd., Tokyo, Japan) with a 13 MHz linear array transducer (UST-5412, Hitachi Aloka 
Medical, Ltd., Tokyo, Japan). During the US examination, the probe will be positioned 
perpendicular to the nerve, and minimal pressure will be applied. A trace method will be used 
for CSA measurements, and the nerve hyperechoic rim will be excluded. Ulnar nerve CSA 
will be measured at the wrist, D4, D2, ME, P2, and P4. In addition, ulnar nerve CSA will be 
measured at the site of maximal CSA (CSAmax) and minimal CSA (CSAmin). Median nerve 
CSA will be measured at the wrist and 10 cm proximally.  
Using the US, UNE will be diagnosed and localized as follows: (1) if a clear constriction (i.e., 
a focal narrowing of at least 2 mm2 relative to the nerve size proximally and distally) will be 
seen distal to the ME then the case will be classified as CTE; (2) if a focal enlargement > 10 
mm2 at or proximal to the ME will be seen then the case will be classified as RCC; (3) in 
cases where CSAmax (> 10 mm2) will be found distal to the ME, but nerve constriction will 
not be seen, then the entrapment site will be taken to be located just distal to the nerve 
enlargement and the case will be classified as CTE.3 In arms with discordant EDx and US 
localisation, US will be given preference. 
 

Randomization and Masking 
The study will have a parallel trial design with a 1:1 allocation ratio, and a trial CONSORT 
diagram will be drawn. CTE and RCC patients will be separately randomized by one of the 
authors (SP), throwing dice as follows: (1) even number – surgical release, and (2) odd 
number – conservative treatment. In patients with bilateral UNE, the more affected arm will 
be randomized. Patients randomized to the surgical arm will be referred to a plastic surgeon. 
All included CTE and RCC patients (also those randomized to surgical release) will be given 
illustrated instructions showing arm positions they should avoid to prevent further ulnar nerve 
damage due to external compression.  
The examiners will be blinded to the patient’s study arm and the findings of other parts of the 
patient evaluation. During follow-up, examiners performing EDx and US examinations will 
be able to see a post-operative scar, but will be unaware of the patient group (i.e., CTE vs. 
RCC). Patients will not be blinded to treatment.  
 
Treatment 
The surgeon will perform division of the HUA 2-3 cm distal to ME in CTE and RCC 
patients.4  
To prevent potential harm due to the delay of surgery, CTE patients randomized to a 
conservative arm will also be seen at 3 and 6 months. In case of clear clinical progression, 
they will be referred for immediate surgery. After 12 months of follow-up, these patients will 
be advised to proceed to surgery. CTE patients randomized to a surgery arm will be seen at 6 
months for calculation of the sample size.  
 
Sample Size Calculation 

The required number of patients in the treatment arms will be determined after the first 20 
patients in both CTE treatment arms have completed 6 months of follow-up. We will calculate 
the proportions of patients perceiving symptom improvement in both treatment arms and a 
standardized difference. For 80% power, the necessary sample size will be determined using a 
nomogram for calculating sample size.5  
 
Primary and Secondary Outcome Measures 
At 12-month follow-up (after surgery or the start of conservative treatment), all patients will 
be evaluated using the same protocol as during the initial evaluation. The primary outcome 
measure of the study will be the change in UNEQ score from baseline at inclusion of patients 
into the study and at 12-month follow-up.  
The secondary outcome measures will be changes in: (1) clinical UNE severity; (2) atrophy of 
the ADM and FDI muscles; (3) strength of the ADM and FDI muscles using the modified 
MRC scale; (4) light touch sensation on the tip of the 5th finger; (5) ulnar MNCVmin across 
the elbow; (6) the amplitude of the ulnar CMAP on stimulation at D4; (7) the amplitude of the 
ulnar SNAP; (8) ulnar nerve CSAmax in the elbow segment; (9) ulnar nerve CSAmin in the 
elbow segment.  
 
Statistics 
All data will be transferred into a Microsoft Excel (Microsoft Corp., Redmond, Washington, 
USA) spreadsheet and analysed using Statistics Kingdom,6 an internet-based statistical 
package. Distribution of numerical variables will be established by the Shapiro-Wilk test. In 
case of non-normal distribution, non-parametric descriptive statistics (i.e., median (25th–75th 
percentile)) and a non-parametric comparison test (Mann-Whitney U) will be used. In case of 
normal distribution, parametric descriptive statistics (i.e., mean (SD – standard deviation)) 

and a parametric comparison test (a two-sample t-test) will be used. Categorical variables will 
be presented as frequencies and percentages. A two-sample Z-test will be used to calculate the 
difference between the two proportions. All tests will be performed at a significance level of 
 = 0.05 (two-sided). 
 
Changes to the protocol  
 
Patients 
No changes. 
 
History and Clinical Neurologic Examination 
Dynamometer results are not presented because they duplicate manual testing without added 
value. 
 
Electrodiagnostic Examination (EDx) 
No changes. 
 
 
Ultrasonography (US) 
The ulnar hand muscle CSA results are not presented because they duplicate clinical testing 
without added value. 
 
 
Randomization and Masking 
No changes. 

 
 
Treatment 
No changes. 
 
 
Sample Size Calculation 
The sample size was calculated using the initial primary outcome measure because we do not 
know the minimal clinically important difference for UNEQ.  
 
 
Primary and Secondary Outcome Measures 
The initial primary outcome measure was the percentage of patients with: (1) no UNE 
symptoms or (2) symptoms markedly improved – only minor symptoms persist at 12 months 
follow-up. However, due to the inclusion of only patients with moderate or severe UNE in the 
present trial, and follow-up of only 12 months, the trial outcomes were much worse than 
expected based on our previous study results. That study also included patients with mild 
UNE and had a much longer follow-up of 2-3 years.7 Only 8 patients (13%) in the CTE arms 
of the present trial reached the primary outcome. Patients also often reported inability to 
reliably compare their current hand symptoms with symptoms one year ago. Therefore, as the 
primary outcome, we reported a comparison of patients’ responses to standard UNEQ at the 
baseline and at 12-month follow-up. This outcome measure was also recommended by the 
authors of a recent Cochrane review.8  

As explained, we deleted instrumental measurements of the FDI muscle CSA using US and 
ADM/FDI muscle strength using a dynamometer, due to duplication of clinical gradings 
without added value, and a large number of secondary outcomes. 
 
 
Statistics 
The large majority of numerical variables were distributed non-normally, and therefore, non-
parametric descriptive statistics (i.e., median (25th–75th percentile)) and a non-parametric 
comparison test (Mann-Whitney U) were used.  
 
 
References: 
1. 
Mondelli M, Padua L, Giannini F, Bibbò G, Aprile I, Rossi S. A self-administered 
questionnaire of ulnar neuropathy at the elbow. Neurol Sci 2006; 27(6): 402-11. 
2. 
O’Brien M. Aids to the Examination of the Peripheral Nervous System. 5 ed. New 
York: Saunders Ltd.; 2010. 
3. 
Omejec G, Podnar S. What causes ulnar neuropathy at the elbow? Clin Neurophysiol 
2016; 127(1): 919-24. 
4. 
Adkinson JM, Chung KC. Minimal-incision in situ ulnar nerve decompression at the 
elbow. Hand Clin 2014; 30(1): 63-70. 
5. 
Altman DG. Clinical trials.  Practical statistics for medical research. 1 ed. London: 
Chapman & Hall; 1991: 440-76. 
6. 
Statistics Kingdom. 2017 (accessed 11.07.2025 2025). 
7. 
Omejec G, Podnar S. Long-term outcomes in patients with ulnar neuropathy at the 
elbow treated according to the presumed aetiology. Clin Neurophysiol 2018; 129(8): 1763-9. 

8. 
Caliandro P, La Torre G, Padua R, Giannini F, Reale G, Padua L. Treatment for ulnar 
neuropathy at the elbow. Cochrane Database Syst Rev 2025; 4(4): Cd006839.