Micronerves in Dupuytren and the Impact of Its Dissection on Recurrence

Dupuytren's Disease Clinical Trial

— Micronerves  

Official title:

Observational Study on Small Nerve Bundles in Dupuytren Disease and the Impact of Its Dissection on Recurrence.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06142929
• Other study ID #: S68137
• Status: Recruiting
• Start date: January 1, 2024
• Est. completion date: January 1, 2026

Study information

• Verified date: January 2024
• Source: Universitaire Ziekenhuizen KU Leuven
• Contact: Ilse Degreef, Prof. Dr.
• Phone: +32 16 33 88 43
• Email: ilse.degreef[@]uzleuven.be
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Dupuytren disease (DD) is a highly prevalent disabling hand disease. Spontaneous fibrosis nodules and strands in the palms of the hand cause finger contractures in disturbing positions and movement restrictions. Finger movement can be restored by surgery (removing the fibrosis tissue), but recurrence is a major problem and this is difficult to treat.

Through microfasciectomy, the presence of small nerve bundles (micronerves) were observed. These nerves are possibly related to the hand fascia, which is the origin of Dupuytren disease. These micornerves and their dissection could play a role in the recurrence of DD. This study will investigate the role of these micronerves in DD, the impact of its dissection on formation of neuromas and on recurrence.

Also, the presence of nerve growth factor (NGF) will be evaluated. The purpose is to provide information on potential neuro-induced fibrosis.

Description:

Dupuytren disease (DD) is a highly prevalent disabling hand disease. Spontaneous fibrosis nodules and strands in the palms of the hand cause finger contractures in disturbing positions and movement restricitions. Finger movement can be restored by surgery (removing the fibrosis tissue), but recurrence is a major problem (reports of >70%) and this is difficult to treat.

Through microfasciectomy, the presence of small nerve bundles (micronerves) were observed in the finger (other than the digital nerves) through microsurgical enlargement. These nerves are possibly related to the hand fascia, which is the origin of DD. Palmaris fascia innervation was recently elucidated in 16 cadavers and recent research had demonstrated that the palmar aponeurosis is densely innervated and contains a variety of sensory corpuscles as wall as free nerve endings.

These micronerves and their dissection could play a role in the recurrence of DD. This thought is substantiated by the fact neuromas (formed by transection of nerves) were found in recurrence DD and nerve damage is generally known to cause fibrosis (as seen in chronic reactive pain syndrome). This study will investigate the role of these micronerves in DD, the impact of its dissection on formation of neuromas and on recurrence.

It's an observational study, investigation 2 groups of patients. Group 1 being patients with primary DD and group 2 patients with recurrence DD. The nerves and possible neuromas will be documented (presence, location, numbers and (unavoidable) micronerve transections) on a standard map and by digital photomicrography in both groups. The first aim is to confirm their presence and their proximity to the DD fibrosis tissue. Secondly, these allocations will be statistically correlated with clinical outcome and compared between the 2 groups. The ultimate goal of these mappings is to develop new surgical techniques that avoid cutting there nerves and/or cut them at preferable locations (away from recurrence, most likely more proximal at a distance to the proximal interphalangeal joints). Hereby an improved surgical technique (microfasciectomy) can possible reduce/avoid neuroma formation, pain and possibly recurrence.

Also, the presence of nerve growth factor (NGF) will be evaluated. The purpose is to provide information on potential neuro-induced fibrosis. NGF is a cell signalling cytokine that was demonstrated earlier to be associated with nerve tissue, neuromas and pain level. It is linked to the alpha-smooth actin expressing myofibroblast, 'activated' connective tissue cells with contractile properties producing collagen strands that cause the finger contractures. Therefore, the presence of NGF and myofibroblast cells crowd around NGF foci will be studied in a biopsy taken per-operatively. Focus will be on the direct environment of the neuromas. The presence of NGF will also be quantified and compared between both groups. It there is a higher amount of NGF in recurrence, there is a possible role for neuro-induced fibrosis and this creates opportunities to select this protein as a target of treatment to improve clinical outcome.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: January 1, 2026
• Est. primary completion date: January 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

Participants eligible for inclusion in this study must meet all of the following criteria:

1. The participant or his/her legally authorized representative voluntary signed the informed consent prior to the first assessment

2. Participants are = 18 years and diagnosed with primary/recurrent Dupuytren disease

3. Included patients are eligible for microfasciectomy

Exclusion criteria:

Participants eligible for this study must not meet any of the following criteria:

1. Patients < 18 years

2. Patient included in an interventional trial with an investigational medicinal product

3. Patients with cognitive impairments, severe rheumatic disease and neurological disorders leading to flexion deformities of the fingers

Related Conditions & MeSH terms

• Dupuytren Contracture
• Dupuytren's Disease
• Recurrence

Intervention

Procedure:
• Microfasciectomy
Using the microscope in Dupuytren's surgery

Locations

Country	Name	City	State
Belgium	Universitaire Ziekenhuizen KU Leuven	Leuven	Vlaams-Brabant

Sponsors (1)

Lead Sponsor	Collaborator
Universitaire Ziekenhuizen KU Leuven

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Presence of neuromas, NGF, aSMA and S100	Presence of neuromas, NGF, aSMA and S100 in Dupuytren nodules after resection.	During surgery/microfasciectomy
Secondary	Presence of micronerves	The presence of micronerves with micro-anatomical description in the digital palmar fascia and their relation to the Dupuytren tissue.	During surgery/microfasciectomy
Secondary	Correlate clinical outcome (motion, pain, recurrence) with these findings (micronerve dissection, presence of neuromas, NGF and aSMA) in both groups	Objective clinical outcome: Range of motion (by goniometry of Distal interphalangeal, Proximal Interphalangeal and metacarpophalangeal joints); Abe. diathesis scoring; Patient reported outcome: QUICK Dash for functionality; Visual Analogue Scale (VAS) questionnaire on satisfaction; Visual Analogue Scale (VAS) questionnaire on pain	pre-operative, post-operative (10 days, 3 months, 12 months)