Neurological Recovery Following NOS-SACD

Paresthesia Clinical Trial

Official title:

Longitudinal Assessment of Neurological Recovery in Patients Following Nitrous Oxide Abuse

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05714917
• Other study ID #: 22NS021
• Status: Not yet recruiting
• Start date: April 1, 2023
• Est. completion date: June 30, 2025

Study information

• Verified date: February 2023
• Source: Nottingham University Hospitals NHS Trust
• Contact: Nikos Evangelou, FRCP, DPhil
• Phone: 07715172966
• Email: nikos.evangelou[@]nottingham.ac.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Nitrous oxide has become an increasingly popular recreational drug amongst young people, particularly at festivals, nightclubs and parties. Considering the drug is not illegal to possess, has low cost in the form of 'whippets' and can be easily purchased online, it has become the second most commonly used recreational drug amongst people aged 16-24 in the UK. However, nitrous oxide is known to irreversibly inactivate the functioning of vitamin B12, a vitamin required for the maintenance and proper functioning of nerves in the spinal cord. Neurological symptoms in this population have been reported in around 3.4% of nitrous oxide users, although the true incidence is expected to be higher as the cases being reported by UK hospitals continues to rise.

Patients may present with adverse neurological symptoms like tingling, weakness, coordination and mobility problems. Currently, studies reviewing the functional recovery of these patients have been limited by a retrospective study design, short follow up duration and being limited to small cohort sizes. This is in part linked to patient non-compliance and non-attendance at follow-up appointments. The investigators will therefore prospectively recruit all patients presenting with these symptoms and continue to collect data relating to their neurological recovery for 12 months. Data collection will be remote to ensure it is of low burden to the participants. This will allow the investigating team and others to fully appraise the severity of these toxic neuropathies and understand how best to manage their follow up.

Description:

This study will take place in selected participating hospitals, including their acute neurology units and emergency departments. Participants presenting to their GP will be referred per standard clinical care with the acute neurology units for study inclusion review. Ideally in all cases the investigating team would prefer for participants to be in hospitals (either directly through A&E or being referred by their GP to the acute neurology service) at the time of study inclusion and for the baseline visit to ensure standard clinical care data can be collected (including MRI, bloods and treatment information including how many Vitamin B12 injections are given at admission and throughout their recovery). Care will be taken over by the neurology team where possible and standard clinical practice for participants with NOS induced neurological damage will be managed and treated as per their own local guidelines. Patients identified to the research team with consultant confirmed NOS-induced neuropathy but have left hospital can still be considered for the study but oral consent will be asked of these participants.

Baseline visit: participants who remain in hospital at the time of study invite will have their concomitant medications, comorbidities and a neurological assessment reviewed in person, blood and MRI results will also be collected from the routine tests that have been performed whilst in hospital. Participants not in the hospital at this point will have this information assessed where possible via the telephone or obtained from their medical records. Individuals without blood or MRI data will not be excluded from the study providing they meet the inclusion criteria.

At the point of consent (written or verbal), recruited participants details (NHS number, name and mobile number) will be securely shared with the coordinating Nottingham University Hospitals NHS Trust center. The Nottingham researcher will then add new participants to the PsychoPy platform which is the University of Nottingham spinoff company that allows remote clinical trial assessments. Each time a participant is added, the platform will automatically generate follow up dates for when each of the subsequent visits are due (baseline visit, 1-month, 3- month, 6-month and 12-month). The Nottingham coordinating team will generate a specific link from this platform each time a participant visit is due, the link will then be sent via text messaging from the coordinating centre to the participants mobile phone. These links can be opened and the visits completed from anywhere provided the participant has internet connection. The content of the visits will include: demographic [baseline visit only], NOS quantification, basic finger tapping task, cognitive function tasks, health questionnaire assessing participants ability to perform simple daily activities, the overall neuropathy limitations scale and the average step count for the last 7-days.

The coordinating team will continue to monitor completed and outstanding visits for all participants and where uncompleted, will send out reminder text messages to the participants.

Our pragmatic approach to perform only remote follow ups was based on the already previously reported high DNA rate in this patient population. All patients will participate in a total of 5 remote visit assessments over the 12-month period.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: June 30, 2025
• Est. primary completion date: March 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 30 Years

Eligibility

Inclusion Criteria:

• Any patient first presented with paraesthesia, weakness, ataxia or gait disturbance with a history of NOS use (age limit 16-30) as of 01/04/2023.

• Patients who can read and write in English, so that they can complete the questionnaires.

• Patients must have received a definitive consultant neurologist confirmed diagnosis of NOS-induced neurological damage. This is possible as all eligible patients will have been reviewed by the neurology team prior to study involvement.

Exclusion Criteria:

•Other causes of previous neuropathy or neurodegeneration indicated.

Related Conditions & MeSH terms

• Avitaminosis
• B12 Deficiency Vitamin
• Neurologic Manifestations
• Neurologic Symptoms
• Nitrous Oxide Abuse
• Paresthesia
• Vitamin A Deficiency
• Vitamin B 12 Deficiency

Intervention

Other:
• Observational study with no interventions
This is an observational study and there will be no clinical interventions.

Locations

Country	Name	City	State
n/a

Sponsors (6)

Lead Sponsor	Collaborator
Nottingham University Hospitals NHS Trust	Barts & The London NHS Trust, Northern Care Alliance NHS Foundation Trust, Sandwell & West Birmingham Hospitals NHS Trust, The Royal Wolverhampton Hospitals NHS Trust, University Hospital Birmingham NHS Foundation Trust

References & Publications (14)

Algahtani H, Shirah B, Abdelghaffar N, Abuhawi O, Alqahtani A. Nitrous oxide recreational abuse presenting with myeloneuropathy and mimicking Guillain-Barre syndrome. Intractable Rare Dis Res. 2020 Feb;9(1):54-57. doi: 10.5582/irdr.2020.01007. — View Citation

Berling E, Fargeot G, Aure K, Tran TH, Kubis N, Lozeron P, Zanin A. Nitrous oxide-induced predominantly motor neuropathies: a follow-up study. J Neurol. 2022 May;269(5):2720-2726. doi: 10.1007/s00415-021-10858-2. Epub 2021 Nov 6. — View Citation

de Medeiros FC, de Albuquerque LA, de Souza RB, Gomes Neto AP, Christo PP. Vitamin B12 extensive thoracic myelopathy: clinical, radiological and prognostic aspects. Two cases report and literature review. Neurol Sci. 2013 Oct;34(10):1857-60. doi: 10.1007/s10072-013-1335-7. Epub 2013 Mar 7. — View Citation

Flippo TS, Holder WD Jr. Neurologic degeneration associated with nitrous oxide anesthesia in patients with vitamin B12 deficiency. Arch Surg. 1993 Dec;128(12):1391-5. doi: 10.1001/archsurg.1993.01420240099018. — View Citation

Garakani A, Jaffe RJ, Savla D, Welch AK, Protin CA, Bryson EO, McDowell DM. Neurologic, psychiatric, and other medical manifestations of nitrous oxide abuse: A systematic review of the case literature. Am J Addict. 2016 Aug;25(5):358-69. doi: 10.1111/ajad.12372. Epub 2016 Apr 1. — View Citation

Kroes AC, Lindemans J, Abels J. [Interaction between nitrous oxide and vitamin B12]. Ned Tijdschr Geneeskd. 1985 Nov 23;129(47):2243-7. No abstract available. Dutch. — View Citation

Omotosho YB, Ying GW, Orji R, Patel H. Recreational Nitrous Oxide-Induced Subacute Combined Degeneration. Cureus. 2022 Mar 22;14(3):e23409. doi: 10.7759/cureus.23409. eCollection 2022 Mar. — View Citation

Patel KK, Mejia Munne JC, Gunness VRN, Hersey D, Alshafai N, Sciubba D, Nasser R, Gimbel D, Cheng J, Nouri A. Subacute combined degeneration of the spinal cord following nitrous oxide anesthesia: A systematic review of cases. Clin Neurol Neurosurg. 2018 Oct;173:163-168. doi: 10.1016/j.clineuro.2018.08.016. Epub 2018 Aug 9. Erratum In: Clin Neurol Neurosurg. 2019 Feb;177:123-124. Abstract corrected. — View Citation

Peirce J, Gray JR, Simpson S, MacAskill M, Hochenberger R, Sogo H, Kastman E, Lindelov JK. PsychoPy2: Experiments in behavior made easy. Behav Res Methods. 2019 Feb;51(1):195-203. doi: 10.3758/s13428-018-01193-y. — View Citation

Schilling RF. Is nitrous oxide a dangerous anesthetic for vitamin B12-deficient subjects? JAMA. 1986 Mar 28;255(12):1605-6. — View Citation

Seed A, Jogia M. Lessons of the month: Nitrous oxide-induced functional vitamin B12 deficiency causing subacute combined degeneration of the spinal cord. Clin Med (Lond). 2020 May;20(3):e7-e9. doi: 10.7861/clinmed.2020-0072. — View Citation

Swart G, Blair C, Lu Z, Yogendran S, Offord J, Sutherland E, Barnes S, Palavra N, Cremer P, Bolitho S, Michael Halmagyi G. Nitrous oxide-induced myeloneuropathy. Eur J Neurol. 2021 Dec;28(12):3938-3944. doi: 10.1111/ene.15077. Epub 2021 Sep 6. — View Citation

Winstock AR, Ferris JA. Nitrous oxide causes peripheral neuropathy in a dose dependent manner among recreational users. J Psychopharmacol. 2020 Feb;34(2):229-236. doi: 10.1177/0269881119882532. Epub 2019 Nov 4. — View Citation

Zheng D, Ba F, Bi G, Guo Y, Gao Y, Li W. The sharp rise of neurological disorders associated with recreational nitrous oxide use in China: a single-center experience and a brief review of Chinese literature. J Neurol. 2020 Feb;267(2):422-429. doi: 10.1007/s00415-019-09600-w. Epub 2019 Oct 26. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improvement in finger tapping task, baseline to month 12	To determine whether patients with NOS-induced neurological damage recover their dexterity function over a 12-month period.	12 months
Secondary	Improvement in cognitive function task, baseline to month 12	To determine whether patients with NOS-induced neurological damage recover their cognitive function over a 12-month period.	12 months
Secondary	Improvement in step counts, baseline to month 12	To determine whether patients with NOS-induced neurological damage recover their average weekly step counts over a 12-month period.	12 months
Secondary	Improvement in I-RODS and ONLS, baseline to month 12	To determine whether patients with NOS-induced neurological damage recover their neuropathy and general health scores over a 12-month period.	12 months

External Links

•   Global Drug Survey 2021