Investigating the effects of nimodipine on spinal reflex measures in humans
| ISRCTN | ISRCTN63413322 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN63413322 |
| Secondary identifying numbers | 514-0849/23-3000 |
- Submission date
- 18/04/2024
- Registration date
- 24/04/2024
- Last edited
- 25/04/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Signs and Symptoms
Plain English summary of protocol
Background and study aims
This study investigates the acute effect of a well-known FDA-approved calcium-channel blocker, nimodipine, on transmission in human spinal reflex pathways involving the ratio of the size of the H-reflex to the size of the M-wave (the H/M-ratio) a method of analyzing changes in motoneuron reflex excitability, the cutaneous reflex, and the stretch reflex. This will locate the action site of nimodipine in the human spinal cord, provide indirect evidence of the existence of Persistent Inward Currents (PICs) in humans, and explore the prospect of nimodipine’s use in future antispasmodic treatment.
Who can participate?
Healthy, adult volunteers (first part of the project) and adult neurological patients with spasticity both aged 18 years old and over
What does the study involve?
People with muscle stiffness will participate in the study where they won't know if they will receive a real medication or a fake one. On the first day, they will take either nimodipine (60mg) or a chalk tablet (the fake one). Then, they will return on another day to try the other option. A doctor who is not part of the study will keep track of who gets what, and will only disclose who received what after the research team has analysed the results in analysis software.
What are the possible benefits and risks of participating?
There are no personal benefits from participating in the study. The overall goal is to get a better understanding of human motor control and reflex behaviour which are often associated with spasticity.
There are very few risks associated with the measurements used in the study. Nimodipine may cause a temporary drop in blood pressure. Baclofen may cause temporary fatigue or nausea.
Where is the study run from?
Panum Institute in Copenhagen and the Glostrup Hospital (Denmark)
When is the study starting and how long is it expected to run for?
August 2019 to August 2025
Who is funding the study?
1. The Novo Nordisk UK Research Foundation (UK)
2. University of Copenhagen (Denmark)
Who is the main contact?
Eva Rudjord Therkildsen (MD PhD student), ertherkildsen@sund.ku.dk
Contact information
Public, Scientific
Blegdamsvej 3B
Copenhagen
2200
Denmark
 ORCID ID |
0000-0003-4797-1050 |
|---|---|
| Phone | +4553551864 |
| ertherkildsen@sund.ku.dk |
Principal Investigator
Blegdamsvej 3B
Copenhagen
2200
Denmark
| ORCID ID |
0000-0002-7634-0218 |
|---|---|
| Phone | +45 31 52 11 31 |
| jlorentzen@sund.ku.dk |
Study information
| Study design | Double-blind randomized crossover controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised cross over trial |
| Study setting(s) | Hospital, Laboratory, University/medical school/dental school |
| Study type | Other |
| Participant information sheet | No participant information sheet available |
| Scientific title | Investigating the acute effect of the calcium-channel blocker, nimodipine, on spinal reflex measures in humans |
| Study objectives | It is hypothesised that the calcium-channel blocker nimodipine will have an acute (~30-90 minutes) effect on spinal reflex measures, hypothetically through inhibition of CaV-mediated persistent inward currents (PICs) in the spinal inter- and motor neurons. Approx. 30-90 minutes after oral tablet intake of nimodipine (Nimotop), this will result in: 1. A decrease in the H/M-ratio 2. A decreased stretch reflex 3. A diminished cutaneous reflex 4. Decreased measures of self-sustained motor neuron firing (e.g., PICs) |
| Ethics approval(s) |
Approved 29/01/2021, The Regional Committee (VEK) - the Capital Region of Denmark (Kongens Vænge 2, Hillerød, 3400, Denmark; +45 38 66 50 00; regionh@regionh.dk), ref: H-20041588 |
| Health condition(s) or problem(s) studied | Healthy individuals and individuals with spasticity |
| Intervention | Healthy volunteers are involved in a double-blinded placebo-controlled cross-over study. All subjects receive either nimodipine (60mg) or baclofen (25mg) on the first experimental day. All subjects return on a different occasion (at least 24 hours after the first experimental day) to receive the other intervention. Individuals with spasticity are involved in the double-blinded placebo-controlled cross-over study. All subjects receive either nimodipine (60mg) or a chalk tablet (placebo) on the first experimental day. All subjects return on a different occasion (at least 24 hours after the first experimental day) to receive the other intervention. An external medical doctor performs the double blinding and will reveal the blinding after all results have been analysed in MatLab. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Not Applicable |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Nimodipine [Nimotop 60 mg tablet], baclofen [25 mg tablet] |
| Primary outcome measure | H/M-ratio measured using surface electromyographic (EMG) analysis of soleus muscle activity before and at 30, 60 and 90 minutes after intervention |
| Secondary outcome measures | The following secondary outcome measures are measures using surface EMG before and at 30, 60 and 90 minutes after the intervention: 1. The size of the stretch reflex during rest and voluntary pre-contraction measured using surface EMG 2. The size of the cutaneous reflex measured using surface EMG from m. tibialis anterior and m. soleus |
| Overall study start date | 01/08/2019 |
| Completion date | 01/08/2025 |
Eligibility
| Participant type(s) | Healthy volunteer, Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 40 |
| Key inclusion criteria | 1. Age 18 years old and over 2. Adults capable of providing informed consent for participation 3. Healthy volunteers will be recruited in the first part of the project 4. In the second part of the project, individuals with symptoms of muscle overactivity (spasticity/spasms/cramps/dystonia) due to CNS damage are recruited |
| Key exclusion criteria | 1. Hypotension (systolic blood pressure <100mmHg) 2. Known impaired liver function, cerebral edema, or significantly increased intracranial pressure 3. Antispastic medication that cannot be paused, or recent botox injections |
| Date of first enrolment | 01/02/2023 |
| Date of final enrolment | 01/02/2025 |
Locations
Countries of recruitment
- Denmark
Study participating centre
Copenhagen
2200
Denmark
Sponsor information
University/education
Blegdamsvej 3B
Copenhagen
2200
Denmark
| Phone | +4535327900 |
|---|---|
| email@sund.ku.dk | |
| Website | https://www.ku.dk/english/ |
"ROR" |
https://ror.org/035b05819 |
Funders
Funder type
Research organisation
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- The Novo Nordisk UK Research Foundation, ovo Nordisk Research Foundation UK, NNUKRF
- Location
- United Kingdom
Government organisation / Universities (academic only)
- Alternative name(s)
- university_of_copenhagen, Københavns Universitet - University of Copenhagen, University of Copenhagen (UCPH), Copenhagen University, Københavns Universitet – Københavns Universitet, University of Copenhagen (KU), Denmark, Københavns Universitet – University of Copenaghen (UCPH), koebenhavns_uni, Københavns Uni, University of Copenhagen, KU, UCPH
- Location
- Denmark
Results and Publications
| Intention to publish date | 01/08/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from Eva Rudjord Therkildsen, ertherkildsen@sund.ku.dk. The datasets are stored in a non-public, secure closed server repository (securefile), specifically for the University of Copenhagen, and RedCap. The data stored on securefile are the EMG data recordings from the experiment. In RedCap information on the type of injury and spasticity are securely stored. Written consent from participants is required and obtained. Data are anonymized (using an ID). The key for the ID is saved on a closed server (the University of Copenhagen). Final data storage plans will be disclosed at a later date. |
Editorial Notes
25/04/2024: Internal review.
19/04/2024: Study's existence confirmed by the Center for Regional Development, The Scientific Ethics Committees.
