Clinical and technical evidence

A literature search was carried out for this briefing in accordance with the interim process and methods statement. This briefing includes the most relevant or best available published evidence relating to the clinical effectiveness of the technology. Further information about how the evidence for this briefing was selected is available on request by contacting mibs@nice.org.uk.

Published evidence

5 studies are summarised in this briefing, including a total of 465 people.

The evidence for gammaCore comprises 3 randomised controlled trials (2 of which compare gammaCore with a sham device); 1 open-label randomised study and a cohort study done in the UK.

Table 2 summarises the clinical evidence as well as its strengths and limitations.

Overall assessment of the evidence

The studies included in table 2 examine the use of gammaCore as a prophylactic treatment for preventing cluster headache and for treating acute pain after the onset of a cluster headache. Several of the studies also separate cohorts into those that have been diagnosed with chronic cluster headache and people diagnosed with episodic cluster headache. The studies recruited relatively large populations given the prevalence of cluster headache. The study design and comparator selection were generalisable to NHS standard practice. The studies suggest that gammaCore is only effective in chronic cluster headache when used as a preventative measure. In episodic cluster headache it is only effective when used as a treatment for acute pain.

Table 2 Summary of selected studies

Goadsby et al. (2018)

Study size, design and location

102 people with cluster headache (30 episodic and 72 chronic).

Randomised, double-blind sham-controlled study.

Location: UK, Netherlands, Germany, Denmark.

Intervention and comparator(s)

gammaCore (used as a treatment for acute pain) and sham device, both arms also had standard care.

Key outcomes

The primary efficacy end point was the proportion of all treated attacks that achieved pain-free status within 15 minutes after starting treatment, without rescue treatment. For the total cohort, there was no significant difference between gammaCore (14%) and the sham device (12%), however, in the episodic cluster headache group gammaCore was statistically significantly superior to sham (48% versus 6%, p=0.01). No significant differences were seen in the chronic cluster headache group.

Strengths and limitations

Sham-controlled study. The study was sponsored by the company.

Gaul et al. (2017)

Study size, design and location

97 people with chronic cluster headache.

Randomised controlled trial.

Location: Germany, Belgium.

Intervention and comparator(s)

gammaCore (used as preventative and acute treatment) plus standard care versus standard care only.

Key outcomes

gammaCore was used 6 times daily to prevent cluster headache. Use of gammaCore in addition to standard care led to a statistically significant reduction in cluster headaches compared with standard care alone (p<0.05). Frequency of headaches reduced by 40% in the gammaCore group compared with standard care and frequency increase of 1% in the standard care only group.

Strengths and limitations

Randomised controlled trial. The study was funded by the company.

Gaul et al. (2015)

Study size, design and location

97 people with cluster headache.

Open-label randomised study.

Location: UK, Belgium, Germany and Sweden.

Intervention and comparator(s)

gammaCore (used as preventative and acute treatment) and standard care (medication).

Key outcomes

People in the standard care plus gammaCore arm (n=45) had a significantly greater reduction in the number of cluster headaches per week versus people in the medication only arm (n=48; 5.9 versus 2.1, respectively). People in the gammaCore arm had a mean therapeutic gain of 3.9 fewer attacks per week (95% CI 0.5–7.2; p=0.02). Response rates were also seen in the gammaCore arm (40% [18/45]) versus people in the control arm (8.3% [4/48]; p<0.001). No serious treatment-related adverse events happened.

Strengths and limitations

Prospective, randomly allocated trial. The study was company sponsored, including having company representatives as co-authors and company sponsored editorial support. The authors stated that gammaCore did not work as an acute treatment.

Silberstein et al. (2016)

Study size, design and location

150 people with either episodic or chronic cluster headache.

Randomised controlled trial using a sham device as control followed by an open-label phase.

Location: US.

Intervention and comparator(s)

gammaCore referred to as nVNS (used as a treatment for acute pain) and sham device.

Key outcomes

The intention-to-treat population comprised 133 subjects: 60 nVNS-treated (eCH, n=38; cCH, n=22) and 73 sham treated (eCH, n=47; cCH, n=26).

The response rate was not significantly different (versus sham) for the total population (response was achieved in 26.7% of nVNS-treated subjects and 15.1% of sham-treated subjects [p=0.1]).

Response rates were significantly higher for gammaCore in the eCH cohort (nVNS, 34.2%; sham, 10.6%; p=0.008) but not the cCH cohort (nVNS, 13.6%; sham, 23.1%; p=0.48). No serious adverse events happened.

Strengths and limitations

Randomised controlled trial. The study was company sponsored, including having company representatives as co-authors and company sponsored editorial support.

Nesbitt et al. (2015)

Study size, design and location

19 people, 11 with chronic cluster headache and 8 with episodic cluster headache. Drug therapy was unsuitable for 7 people in the study.

Open-label observational cohort study (audit).

Location: UK and Republic of Ireland.

Intervention and comparator(s)

gammaCore for both prophylactic and acute use.

Key outcomes

15 patients reported an improvement; 4 reported no change.

47% of cluster headaches were aborted within an average of 11±1 minutes of using gammaCore. Ten patients reduced their acute use of high-flow oxygen by 55% with 9 reducing triptan use by 48%. Prophylactic use of gammaCore resulted in a substantial reduction in estimated mean attack frequency from 4.5/24 hours to 2.6/24 hours (p<0.0005).

Strengths and limitations

Small audit study. The study was supported by a grant from the company.

Abbreviations: cCH: chronic cluster headache, CI: confidence interval, eCH: episodic cluster headache, nVNS: non-invasive vagus nerve stimulation

Recent and ongoing studies

No ongoing or in-development trials were identified.