Double Upper Limb Allograft: Intervention and Clinical Evaluation. A Pilot Study of 5 Cases

Study Overview
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Brief Summary
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The case of patients with amputation of forearm on one side and arm on the other is particularly interesting to study because in this situation of handicap greater than a double amputation in forearm. We should bring a functional benefit to the patient with the transplant of forearm and this situation allows to have the best possible control to compare the result of the transplant of arm to that of forearm because it is realized at the same patient. Amputation of both arms deprives patients of an elbow what establishes a major factor of limitation of autonomy and makes patients totally dependent for the realization of the essential gestures of the current life requiring the prehension (dress, dressing, food, hygiene of the elimination). The various equipments are not always adaptable and usable. Psychologically, an amputation in arm is unanimously considered as an infringement very badly accepted of the physical integrity and establishes a major handicap factor of family, professional and social exclusion. The results of this study should allow a better appreciation of indications and modalities of care of biamputed patients with at least one lesion level above the elbow. This clinical research will determine the potential place of a reconstructive surgery as allograft in biamputed patients on the basis of functional results and assessment of disorders of the body schema perception.

Official Title
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Double Upper Limb Allograft: Intervention and Clinical Evaluation. A Pilot Study of 5 Cases

Conditions
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Bilateral Amputation of Upper Limb

Intervention / Treatment
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* Procedure: Double upper limb allograft


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women Bilateral amputation of upper limb regardless of the nature of the injury (crush, tearing, cutting, infectious such as purpura fulminans...) except for tumor diseases Lesion level: The non-transplant patients-free immunosuppressive therapy: bilateral amputation of upper limb with at least one lesion level above the elbow. Higher amputation level is fixed to the upper 1/4 of the arm to allow for a recovery of active flexion of the elbow against gravity. For organ transplant patients (other than hand or upper extremity: ex liver, kidney) and already under bi - or tri-therapy immunosuppressive : bilateral amputation of upper limb with at least one lesion level above the elbow. The top level of amputation may be above the upper 1/4 of the arm especially if body image disorders dominate the complaint of the patient. Period since amputation of at least 6 months Failure of all currently available (including the prosthetic) support modalities Psychological maturity: absence of serious disorder of the personality or chronic disorders of mood reported by psychiatrists of the team using tests for the assessment of personality, committed and voluntary patients Signature of the free and informed consent form Exclusion Criteria: Mono-amputee patient Patients with brachial plexus lesions Patients with vascular disorders likely result in thrombosis Active smoking patients Patients in an emergency medical situation Antecedent of malignant tumor in remission for less than 5 years Patients with malignant tumor Patients with a American Society of Anesthesiology (ASA) score > 3 Patients with glomerular filtration < 60 ml/min Patients with severe hypertension : Systolic Blood Pressure (SBP) > 140 mmHg and Diastolic Blood Pressure (DBP) > 90 mmHg

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bilateral amputation of upper limb<br>Patients with bilateral amputation of upper limb will receive a double upper limb allograft | Procedure: Double upper limb allograft<br>* Patients with bilateral amputation of upper limb will receive a double upper limb allograft<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in functional recovery from baseline to 5 years after the transplant of upper limbs | Functional results assessed by a multidimensional evaluation: A general clinical assessment An analytical assessment: Articular : Total Active Motion (TAM) as a percentage of Total Passive Motion (TPM) Muscle: manual muscle strength testing and quantitative by Jamar dynamometers A sensory and proprioceptive balance: sensitivity on mapping of WINN-PARRY, with assessment of sensitivity of protection and discriminative touch mobile and static touch, Moving Two Points Distance, Static Two Points Distance (Weber test). A functional balance based on: DASH test, Carroll test, balance of 400 points, tests of independence and Hand Transplantation Score System (HTSS) Impact on quality of life: measured by the Medical Outcome Study Short Form-36 (MOS SF-36) | Before the transplant, then at 6 months, 1, 2, 3, 4 and 5 years after a double transplant of upper limbs. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients body image perception | An auto-questionnaire based on 3 questions answered by level type Likert (not at all agree, disagree, neutral, agree, quite agree) • Questionnaire Fragebogen zum KorperBild 20 (FKB-20) | To be measured before the transplant, then at 6 months, 1, 2, 3, 4 and 5 years after transplant | 
| Patients' self-esteem | The Rosenberg self-esteem scale will be used to evaluate patients amputated and then grafted. | To be measured before the transplant, then at 6 months, 1, 2, 3, 4 and 5 years after transplant | 
| Brain plasticity post-transplant | The degree of reorganization of the primary motor cortex will be measured by the assessment of re-innervation and the integration of the graft to the body schema by cerebral functional MRI with psychological tests. | Before intervention, then 3, 6, 12, 18 and 24 months after the transplant. | 
| Acute rejection rate in post-transplant period | To be appreciated by inflammatory signs (erythema) at the clinical examination. The diagnosis of acute rejection will be confirmed on the basis of histological results. | To be measured at 6 months, 1, 2, 3, 4 and 5 years after transplant | 
| Chronic rejection rate in post-transplant period | To be approached by various exams: MRI CT scan of segments transplanted Micro-Doppler looking for intimal hypertrophy An endovascular echography of vessels above the fold of the elbow Capillaroscopy Arteriography will be carried out at 5 years to better appreciate achieving vascular grafts Histological study of the skin and deep tissues. | Throughout the five years of follow-up | 
| Walking analysis in posturography | The walking analysis is a non-invasive examination which consist in recording the movements by a roptoelectronic device. This system captures the three-dimensional position of retro-reflective markers placed on the body. Once analyzed, this information allows getting data quantified on movements. | To be carried out before the transplant, then at 6 months, 1, 2, 3, 4 and 5 years after transplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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upper limb, Bilateral amputation, allograft