SAFETY OF SPLENIC NERVE STIMULATION IN PATIENTS WITH RA (GAL1039_V10)
Research type
Research Study
Full title
A SINGLE ARM PILOT STUDY TO EVALUATE THE SAFETY AND FEASIBILITY OF SPLENIC NERVE STIMULATION IN PATIENTS WITH RHEUMATOID ARTHRITIS USING AN ACTIVE IMPLANTABLE DEVICE
IRAS ID
293980
Contact name
Stacy Skare
Contact email
Sponsor organisation
Galvani Bioelectronics
Clinicaltrials.gov Identifier
Duration of Study in the UK
7 years, 1 months, 31 days
Research summary
Summary of Research
The Galvani Splenic Neuromodulation System for treatment of rheumatoid arthritis (RA) will be assessed under Protocol GAL 1039 in adult subjects with moderate to severely active RA who have experienced prior inadequate response to at least two biologic DMARDs and/or JAK-inhibitors (JAKis). The study will be an open-label single arm study to be conducted in a single center in Glasgow, Scotland. Up to five RA patients will be implanted with the device and following a recovery period receive neurostimulation for 12 weeks. If patients do not adequately respond to stimulation the number of stimulations may be increased, including introducing stimulation during the night.
The primary objective of this study is to assess safety and tolerability of: (a) Laparoscopic surgical implantation of the Galvani System and (b) splenic neurovascular stimulation using this device, through the 12-week study period. The secondary objectives include to assess effect on biomarkers, evaluate device usability and performance, and assess perception of therapy. Main exploratory objectives include to evaluate the efficacy of splenic neuro vascular bundle stimulation on clinical signs and symptoms and to assess a large set of additional biomarker responses. Upon completion of the of Period 1 (Day 84), participants will en roll in Period 2, the long-term follow-up of which the main purpose is to evaluate the safety, tolerability and efficacy of chronic implantation and active stimulation with the Galvani System.Summary of Results
Joint inflammation and other symptoms in patients with RA cannot always be successfully treated with currently available medications. Laboratory research has shown that stimulation of the splenic nerve (a nerve in your abdomen) can inhibit inflammation.
The main purpose of the study was to determine whether keyhole surgery to implant the investigational device ("implantation"), and subsequent stimulation of the splenic nerve, was safe in humans. Additionally, checks were made to confirm whether the investigational device was working correctly. A second research goal was to determine if splenic nerve stimulation could inhibit joint inflammation and other symptoms of RA.
Five patients who were older than 22 years and had moderate to severe RA participated in this study. The study showed that placing the study device and stimulating the splenic nerve was safe in these 5 participants. The stimulation was well tolerated. Because the study was done in a small group of participants, no definitive conclusions could be made in relation to the effectiveness of the splenic nerve stimulation.2. General information about the study
Each participant went through different periods during the study.
Screening (4–6 weeks): A comprehensive health test was performed to verify that the participant met the inclusion and exclusion criteria of the study (see below). In addition, tests were performed to check the participant was healthy enough to undergo surgery.Surgery & recovery (4 weeks): A surgeon used a minimally invasive procedure (laparoscopic or "keyhole" surgery) to place the investigational device inside the body. The device remained turned off for one month (no stimulation) whilst the participants fully recovered from surgery.
Period 1, Active stimulation (12 weeks): The device was turned on, and the level of stimulation was slowly increased over a number of hospital visits to a dose that was well tolerated by the participant. The study device was then programmed to provide deliver electrical signals (stimulation) to the splenic nerve 6 times a day. After 6 weeks, if they wanted, the participant could then choose to increase the number of stimulations per day from 6 to 12, together with the option to receive stimulation during the night.
Period 2, Long-term follow-up (Up to 5 yrs): At the end of Period 1, all participants were followed in Period 2 for what was to be a maximum of 5 years. This was done to assess the safety and effects of the study device and the stimulation in the long term. During this period the physician, in consultation with the participant, could turn off the stimulation or combine stimulation with drugs to treat the RA.
The study was conducted in the Scotland and The Netherlands. Participants were implanted with the study device between November 2021 and November 2024.
On April 24, 2026, the Sponsor, Galvani Bioelectronics, stopped the study with the investigational device. This was only done for business reasons, and not because there was a problem with the safety or the performance of the device. At that time, all participants had completed the first period (Period 1) of 12 weeks of stimulation. This was the most important period for the study's research goals. Participants were followed at the time of study discontinuation in Period 2 where safety and effectiveness were further investigated. Galvani Bioelectronics thanks the participants for their involvement in the study.
What was the Main Objective of the Study?
The main objective of this trial was to investigate whether it was possible to place the investigational device in the abdomen with a so-called "keyhole surgery" and whether it was safe to stimulate the splenic nerve.
The researchers collected any participants' side effects and determined if they were caused by the surgery, the study device, the stimulation, or something unrelated to the study. In addition, a questionnaire was used to understand the sensations felt by the participants during stimulation.
Because this study was the first study in which the investigational device was implanted in humans, the most important thing was to evaluate the safety. Additionally, researchers determined whether there was a positive effect of the splenic nerve stimulation on disease activity. This was done by comparing disease activity at the beginning of the study with disease activity at different time points after the start of stimulation.
In addition, patient-reported outcomes were collected using questionnaires with questions related to, for example, pain, but also about daily life (e.g. climbing stairs, opening a jar yourself).
Because in this study all 5 participants were stimulated ("open-label" study), the effect of the stimulation could not be compared with a control group.3. Who could participate in the study?
In total 5 patients (maximum permitted; 3 women and 2 men) participated in this study, 2 in Scotland and 3 in the Netherlands; their average age was approximately 63 years.
Inclusion & Exclusion Criteria
Main conditions for participation in the study (inclusion criteria) were:
• Older than 22 years;
• Moderate to severe RA;
• Have not responded well to at least two standard biologic treatments or advanced medications (such as JAK inhibitors).
Important conditions for exclusion (exclusion criteria) were:
• Other uncontrolled inflammatory diseases;
• Other implanted electrically active medical devices;
• Cancer in the last five years;
• A belly wall thickness greater than 2.5 cm;
• Major cardiovascular or surgical risk.4. Which device was examined?
The investigational device, the Galvani neuromodulation system, was developed by Galvani Bioelectronics to be placed in the abdomen around the splenic nerve by means of keyhole surgery. The part that was placed around the splenic nerve was connected by a wire to a battery-powered electronics unit that was placed under the skin. The electronics unit could be programmed in such a way that the splenic nerve was briefly stimulated at fixed times of a day (the 'therapy'). The electronics unit could also store data, for example how often the stimulation was given and at what time. Outside the body, a remote control (a smartphone) and a charger were used. The remote control was used to check the electronics unit (e.g. whether the battery of the electronics unit was still sufficiently charged). The charger was placed on the skin above the electronics unit to charge it for about 30 minutes a week. The study doctor was able to set up the study device (how often the nerve was stimulated) and check whether the study device still working properly by using their programmer (a tablet computer).
5. What were the side effects?
Throughout the study, adverse events related to surgery, the investigational device itself, or stimulation therapy were examined.
All implantation surgeries were performed successfully. Recovery after surgery was successful, and no serious adverse events or serious adverse effects of the investigational device or surgery were found.
There were 4 adverse events in 3 participants that were related to the implantation surgery. An adverse event was called an investigational device-related adverse event. An adverse event in one participant occurred when the research device came off the splenic nerve during placement and damaged a blood vessel, resulting in a small amount of bleeding. The bleeding was quickly stopped, and the participant had no further consequences. The other three adverse events were related to pain and swelling at the site where the small incisions for keyhole surgery were placed. These side effects disappeared after a few weeks, with one participant taking pain relief for a week.
In total, there were 3 adverse events in 2 participants over all periods that may have been related to the splenic nerve stimulation. These side effects were mild to moderate and disappeared, with one requiring a small reduction in the intensity of stimulation.
There was a problem with one investigational device in the first participant. At the end of Period 1, during the visit to the hospital, it was seen that the investigational device was no longer working properly. The device was then turned off, and the participant was further monitored for safety in Period 2 but could no longer receive splenic nerve stimulation. Following investigation into the cause of the malfunction of the investigational device in this participant, minimal changes to the device were made. The revised device was then implanted in the following 4 participants and worked without issue.
The stimulation therapy was well tolerated. The stimulation dose was slowly increased over several hospital visits. If the participant felt a stimulation that was unpleasant, it was lowered a step until it was no longer unpleasant. Each participant was stimulated with their own maximum dose that was comfortable for them.
There were no serious adverse events (e.g. adverse events requiring hospitalisation) related to the surgery, study device, or stimulation. Also, no participant died because of an adverse event.6. What are the main results of the study?
The first open-label study with Galvani's research device has shown:
• That the placement of the study device with keyhole surgery is feasible and well tolerated by the participants.
• No serious side effects were seen that are related to the surgery, investigational device or stimulation. The safety risk is considered acceptable on the basis of this study.
• The splenic nerve stimulation was well tolerated.
• The findings of the effectiveness on disease activity were mixed. Two participants showed improvements in disease activity with stimulation alone or in combination with another drug for RA. The other participants showed limited or no effect. Because this is a small group of participants in this pilot study, no definitive conclusions can be drawn about the clinical effectiveness.
• In the participant who showed the greatest effect with splenic nerve stimulation alone on disease activity, their pain was also greatly reduced.7. How did this study help patients and researchers?
The positive findings in this study regarding the safety, tolerance of the stimulation and the effect of the stimulation on disease activity in some participants, show that it is important to do further research.
These studies should be done in larger groups of RA patients. In addition, a control group must be added where some participants are not stimulated in the first period to be able to directly compare the results for safety and effectiveness with the treated group of patients. In future studies, the stimulation dose could also be further optimised and it can be investigated which patients respond well to this new therapy. This could lead to a new therapy for patients with difficult to treat RA who currently have only a few options for controlling disease activity.8. Are there any plans for future studies?
At the moment, no further studies are planned.9. Where can I find more information about the study?
More information about this study can be found at https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fclinicaltrials.gov%252Fstudy%252FNCT04955899%2FNBTI%2FU9fGAQ%2FAQ%2Fda877b25-a2a2-4d45-b481-1c8c2828f5f5%2F2%2F0j8voKvdr6&data=05%7C02%7Capprovals%40hra.nhs.uk%7Cc04504a9cf24409ca49608dee6fc2f92%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C639202167984426682%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=Ud1NdNB208Jqx2GZzt1to%2FvXG%2F5jHU%2B9JQ05GUgs4LI%3D&reserved=0REC name
South East Scotland REC 02
REC reference
21/SS/0009
Date of REC Opinion
8 Mar 2021
REC opinion
Further Information Favourable Opinion