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CTRI Number  CTRI/2023/08/056849 [Registered on: 23/08/2023] Trial Registered Prospectively
Last Modified On: 01/09/2023
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Surgical/Anesthesia 
Study Design  Randomized, Parallel Group, Active Controlled Trial 
Public Title of Study   Comparison of Surgery versus cervical collar treatment in Hirayama Disease (a medical condition with weakness and wasting of arms and/or hands) 
Scientific Title of Study   Posterior cervical fixation versus long-term cervical collar for management of Hirayama Disease: Prospective randomized open blinded endpoint (PROBE), phase III study 
Trial Acronym  - 
Secondary IDs if Any  
Secondary ID  Identifier 
AC-60  Other 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Deepti Vibha 
Designation  Professor 
Affiliation  All India Institute of Medical Sciences 
Address  Room number 707, Neurosciences Center Department of Neurology

South West
DELHI
110029
India 
Phone  011-26594485  
Fax    
Email  deeptivibha@aiims.edu  
 
Details of Contact Person
Scientific Query  
Name  Deepti Vibha 
Designation  Professor 
Affiliation  All India Institute of Medical Sciences 
Address  Room number 707, Neurosciences Center Department of Neurology

South West
DELHI
110029
India 
Phone  011-26594485  
Fax    
Email  deeptivibha@aiims.edu  
 
Details of Contact Person
Public Query  
Name  Deepti Vibha 
Designation  Professor 
Affiliation  All India Institute of Medical Sciences 
Address  Room number 707, Neurosciences Center Department of Neurology

South West
DELHI
110029
India 
Phone  011-26594485  
Fax    
Email  deeptivibha@aiims.edu  
 
Source of Monetary or Material Support  
All India Institute of Medical Sciences, New Delhi, India 
 
Primary Sponsor  
Name  All India Institute of Medical Sciences 
Address  Departments of Neurology and Neurosurgery, AIIMS, New Delhi 
Type of Sponsor  Government medical college 
 
Details of Secondary Sponsor  
Name  Address 
Kanwaljeet Garg  Department of Neurosurgery, AIIMS, New Delhi 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Prof Deepti Vibha  All India Institute of Medical Sciences (AIIMS), New Delhi  Departments of Neurology, Neurosurgery and Neuroradiology, AIIMS, New Delhi
South West
DELHI 		 01126594485

deeptivibha@aiims.edu 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
AIIMS Ethics Committee  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: G128||Other spinal muscular atrophies and related syndromes,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  Cervical collar  24 hours cervical collar treatment will be provided to the medical arm 
Intervention  Posterior cervical fixation surgery  Posterior cervical fixation surgery will be done under GA to prevent dynamic flexion ischemia in progressive disease 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  50.00 Year(s)
Gender  Both 
Details  (1) Age ≥ 18 years
(2) Patients with Hirayama disease as per the following criteria (All of the following):
a. Clinical evidence of wasting and weakness confined to one limb (EMG evidence of denervation in the opposite limb will not be a reason for exclusion)
b. Progressive course, or initial progression followed by stationary course; and
c. No evidence of a compressive lesion of the spinal cord.
(3) Disease duration of ≤4 years
(4) Progression of clinical symptoms in the past six-months
 
 
ExclusionCriteria 
Details  Any of the following:
(1) Refusal to consent for randomization.
(2) Not willing to come for three- and six-months follow-up.
 
 
Method of Generating Random Sequence   Permuted block randomization, variable 
Method of Concealment   Sequentially numbered, sealed, opaque envelopes 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
1) To determine & compare the efficacy of posterior cervical fixation versus cervical collar in patients with Hirayama disease in terms of Odom’s criteria at six months after randomization.   Six months 
 
Secondary Outcome  
Outcome  TimePoints 
1) To determine & compare the efficacy of posterior cervical fixation versus cervical collar in patients with Hirayama disease in terms of Odom’s criteria at three months after randomization.  Three months 
2) To compare MRI DTI parameter in two groups  Six months 
3) Compare clinical & electrophysiological features in two groups  Six months 
 
Target Sample Size   Total Sample Size="80"
Sample Size from India="80" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)   31/10/2023 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="3"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  		 Open to Recruitment 
Recruitment Status of Trial (India)  Open to Recruitment 
Publication Details   N/A 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary  

1.      Research Hypothesis:

The surgical intervention is superior to neck immobilization using a cervical collar in Hirayama disease in terms of clinical and radiological improvement at six months after surgery.

2.      Background and Rationale of the Study

Hirayama disease (HD), also known as juvenile muscular atrophy, or monomelic amyotrophy (MMA) affecting the upper extremity, is a special neurological disorder first brought to attention by a Japanese neurologist, Keizo Hirayama in 1959.(5) In India, similar cases, as well as variants, have been published (6). The disease predominantly affects males in their second decade (3) and leads to considerable morbidity in their economically productive stage of life. The long-term follow-up studies of HD have shown that the patients progressed for 4-5 years before stabilization of the disease but with significant residual neurological deficits.(7) The putative etiology described is dynamic compression of the cervical dural canal in flexed neck posture causing dynamic compression and ischemia of lower cervical cord (5), while post-infectious (3) and genetic (8,9) etiologies have also been postulated.

Although several surgical interventions are described (4), there is a glaring evidence-practice gap in management. The evidence of surgical benefit is limited to case series(10–12), or case-control studies. (2) In the modified Delphi technique to understand the diagnosis and treatment of HD, 40.5% of experts opted for surgical treatment when the disease duration is less than 4 years and there has been disease progression in the past 6 months, while 38.1% opted for conservative treatment and 21.4% were neutral.(13) A recent case-control study (2) found 76% in the surgical group had clinical improvement while none in the conservative group. This huge effect size should be exploited to benefit young patients, by generating a level I evidence. 

The rationale of surgical intervention in patients with HD is to immobilize the spine in extension to prevent compression over the cervical spinal cord, which occurs in flexion. The use of several surgical approaches in patients with HD have been described in the literature. The rate of neurological improvement has been found to be similar between anterior and posterior surgical approaches in a recent meta-analysis.(4) It has shown that posterior cervical fixation carries the least risk of blood loss. Hence, we have chosen this surgical approach.

References: 

1.         Wang H, Tian Y, Wu J, Luo S, Zheng C, Sun C, et al. Update on the Pathogenesis, Clinical Diagnosis, and Treatment of Hirayama Disease. Front Neurol [Internet]. 2022 [cited 2022 Mar 9];12. Available from: https://www.frontiersin.org/article/10.3389/fneur.2021.811943

2.         Thakar S, Arun AA, Rajagopal N, Aryan S, Mohan D, Vijayan JE, et al. Outcomes after Cervical Duraplasty for Monomelic Amyotrophy (Hirayama Disease): Results of a Case–Control Study of 60 Patients. J Neurosci Rural Pract. 2021 Sep 22;12(4):642–51.

3.         Vibha D, Behari M, Goyal V, Shukla G, Bhatia R, Srivastava AK, et al. Clinical profile of Monomelic Amyotrophy (MMA) and role of persistent viral infection. J Neurol Sci. 2015 Dec 15;359(1–2):4–7.

4.         Bohara S, Garg K, Mishra S, Tandon V, Chandra PS, Kale SS. Impact of various cervical surgical interventions in patients with Hirayama’s disease—a narrative review and meta-analysis. Neurosurg Rev. 2021 Dec;44(6):3229–47.

5.         Hirayama K, Tomonaga M, Kitano K, Yamada T, Kojima S, Arai K. Focal cervical poliopathy causing juvenile muscular atrophy of distal upper extremity: a pathological study. J Neurol Neurosurg Psychiatry. 1987 Mar 1;50(3):285–90.

6.         Gourie-Devi M, Suresh TG. Madras pattern of motor neuron disease in South India. J Neurol Neurosurg Psychiatry. 1988 Jun;51(6):773–7.

7.         A N, M GD, K T, Ah R. Monomelic amyotrophy: clinical profile and natural history of 279 cases seen over 35 years (1976-2010). Amyotroph Lateral Scler Front Degener [Internet]. 2014 Sep [cited 2022 Mar 14];15(5–6). Available from: https://pubmed.ncbi.nlm.nih.gov/24853410/

8.         Atchayaram N, Vasudev MK, Goel G. Familial monomelic amyotrophy (Hirayama disease): two brothers with classical flexion induced dynamic changes of the cervical dural sac. Neurol India. 2009 Dec;57(6):810–2.

9.         Lim YM, Koh I, Park YM, Kim JJ, Kim DS, Kim HJ, et al. Exome sequencing identifies KIAA1377 and C5orf42 as susceptibility genes for monomelic amyotrophy. Neuromuscul Disord NMD. 2012 May;22(5):394–400.

10.       Lu F, Wang H, Jiang J, Chen W, Ma X, Ma X, et al. Efficacy of anterior cervical decompression and fusion procedures for monomelic amyotrophy treatment: a prospective randomized controlled trial: Clinical article. J Neurosurg Spine. 2013 Oct 1;19(4):412–9.

11.       Song J, Cui ZY, Chen ZH, Jiang JY. Analysis of the Effect of Surgical Treatment for the Patients with Hirayama Disease from the Perspective of Cervical Spine Sagittal Alignment. World Neurosurg. 2020 Jan 1;133:e342–7.

12.       Zhang H, Wang S, Li Z, Shen R, Lin R, Wu W, et al. Anterior Cervical Surgery for the Treatment of Hirayama Disease. World Neurosurg. 2019 Jul 1;127:e910–8.

13.       Lyu F, Zheng C, Wang H, Nie C, Ma X, Xia X, et al. Establishment of a clinician-led guideline on the diagnosis and treatment of Hirayama disease using a modified Delphi technique. Clin Neurophysiol Off J Int Fed Clin Neurophysiol. 2020 Jun;131(6):1311–9.

14.       Broekema AEH, Molenberg R, Kuijlen JMA, Groen RJM, Reneman MF, Soer R. The Odom Criteria: Validated at Last: A Clinimetric Evaluation in Cervical Spine Surgery. J Bone Joint Surg Am. 2019 Jul 17;101(14):1301–8.

15.       Sletten DM, Suarez GA, Low PA, Mandrekar J, Singer W. COMPASS 31: A Refined and Abbreviated Composite Autonomic Symptom Score. Mayo Clin Proc. 2012 Dec 1;87(12):1196–201.

16.       Gourie-Devi M, Suresh TG, Shankar SK. Monomelic Amyotrophy. Arch Neurol. 1984 Apr 1;41(4):388–94.

 
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