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Professor Dirk De Ridder, a world-leading expert in tinnitus, is investigating the combined effect of ketamine and brain stimulation on tinnitus loudness and distress, as part of a new phase 1/2 clinical trial.

The aim of the study is to determine if low dose ketamine, through its effects on brain plasticity, is able to catalyze transcranial electrical stimulation, and reduce tinnitus severity as a result.

Starstim 32 neuroelectric headset for ketamine tinnitus trial — Behold… The Starstim 32 headset (device) that will be used alongside ketamine (drug), for this device/drug combination therapy trial.

A total of 24 participants with chronic tinnitus will get a chance to receive treatment with the experimental drug/device combination therapy, at the University of Otago Dunedin School of Medicine, in New Zealand. The treatment will be delivered twice, 10 days apart.

ketamine molecule — Ketamine molecule. Not quite as cool-looking as the headset device. But still, an essential part of the combo therapy.

Inclusion criteria: Adults aged between 18-70 years with constant subjective tinnitus and a grade of 3 or higher (considered “moderate to severe”) on the tinnitus questionnaire.

The trial (Registration number: ACTRN12621000119897p), titled “Effect of ketamine and concomitant multi-target high definition transcranial electrical stimulation on tinnitus loudness and distress in adults- A feasibility and safety study”, is registered prospectively on the Australia New Zealand Clinical Trials Registry.

As of May 12, 2021, it is unclear whether or not anyone has been enrolled (yet) or if the coordinators have begun recruiting participants.

The anticipated date of first enrollment is listed as February 15, 2021. However, according to the provisional study record, the trial’s ethics application is still awaiting approval.

Here is some more information, taken directly from the provisional study record (emphasis/formatting ours):

Ketamine and High Definition, Trancranial Infraslow Pink Noise Stimulation (HD-tIPNS)

The intervention arm will receive a low dose of subcutaneous ketamine (0.5mg/kg) as a bolus, from a clinician experienced in administration. This will be followed by HD-tIPNS administered for a single session of 30 minutes duration, beginning ~25 minutes after ketamine delivery, by a researcher experienced in administering neuromodulation techniques.

A battery-driven wireless 32 channel transcranial current stimulator (Starstim32 TCS®, Neuroelectrics) will be used to deliver stimulation while the participants are comfortably and quietly seated. Simulation [sic] is delivered by AgCl electrodes placed in the international 10-20 arrangement, secured in a neoprene cap (see Neuroelectrics website for headset image). For the active treatment group, the stimulation will be delivered at a current strength of maximum of 2mA for 30min, with 60s ramp up and ramp down at the beginning and end of each stimulation session, with continuous stimulation in between. For sham stimulation, to create an identical skin sensation to the active stimulation, the current will be applied for a 60s ramp up (0-2mA) and 60s ramp down (2-0mA) at the beginning and the end of each stimulation session, without any current for the remainder of the stimulation period.

This Intervention will be delivered twice, spaced 10 days apart. Intervention duration will be a total of 2 hours in length to allow for safety monitoring. After a 20 day washout, both groups will transition to the intervention, delivered twice again, 10 days apart.

The delayed start occurs as follows: Participants can be allocated to start with Ketamine + Active Stimulation or Ketamine + Sham Stimulation. Both the sham stimulation and the active stimulation groups will receive active stimulation after the 20 day washout (the Ketamine + Sham stimulation is the active control). Therefore the Ketamine + Sham stimulation (Active control) receives a delay to the start of active intervention.

Participants will undergo treatment at the Department of Psychological medicine laboratory at the Dunedin School of Medicine, University of Otago.

Intervention [1] Treatment: Drugs

Intervention [2] Treatment: Devices

Comparator / control treatment: Participants in the control arm will receive a low dose of subcutaneous ketamine (0.5mg/kg) as a bolus, from a clinician experienced in administration. This will be followed by Sham stimulation, designed to create identical skin sensations to active stimulation. Participants will use identical equipment to that of the active group, and will receive a short dose of the treatment protocol, mimicking the initial tingling/prickling commonly experienced with Transcranial electrical stimulation.

Primary outcome
Tinnitus Functional Index (TFI). The TFI has eight subscales that address the intrusiveness of tinnitus, the sense of control the patient has, cognitive interference, sleep disturbance, auditory issues, relaxation issues, quality of life, and emotional distress. This provides an overall measure of how much of a problem tinnitus is for participants (severity).

Adults aged between 18-70 years with constant subjective tinnitus and a grade of 3 or above on the tinnitus questionnaire.

Minimum age 18 Years

Maximum age 70 Years

Gender Both males and females

This article will be updated as more information is added to the study record.

For additional updates related to this ketamine/brain stimulation combination therapy (and other experimental not-yet-available tinnitus treatments), subscribe to the Tinnitus Treatment Report newsletter (email updates). It’s free, there’s no spam or sneaky promotional emails, and your information is kept private.

References

Questions? Comments? Feedback? Send an email to michael@urgentresearch.com and say hello.

A new phase 3 clinical trial for tinnitus has begun recruiting at Mazandaran University of Medical Sciences, a top medical university in Iran.

Researchers will investigate whether or not a combination of bitter almond oil and cinnarizine can reduce tinnitus severity in patients with chronic tinnitus.

The title of the study is “The Efficacy of bitter almond oil on the severity of chronic tinnitus.”

Iran bitter almond oil tinnitus study — This study was found “hiding” on a little-known Iranian clinical trial registry. We verified it by cross-referencing the study’s unique registration identifiers in a WHO database as well as the Cochrane Central Register of Clinical Trials.

Participants in the treatment group will receive a combination of bitter almond ear drops and cinnarizine tablets, twice daily (every 12 hours), for one month.

Tinnitus severity will be measured ~~thrice~~ three times: 1) immediately before treatment begins, 2) after two weeks of treatment, and 3) after 4 weeks of treatment, using VAS and THI scores.

This trial was registered on February 16, 2021 and will enroll up to 70 patients with doctor-confirmed chronic tinnitus, between the ages of 17 and 75, male and/or female.

As of March 1, 2021, recruiting for this study was set to begin on March 5, 2021. No reason to assume that date has changed. But we will update this post as we get more information.

As for the treatment itself – a unique combination of ear drops and tablets – here is some very basic background information:

More information on bitter almond oil will follow. For now, an important warning:

WARNING: “bitter almond oil” might sound like a harmless natural ingredient, but in reality it is associated with some extremely serious chemical compounds (i.e. cyanide). Needless to say, there is NO safe (or legal) do-it-yourself approach to copying this trial. Or any trial, for that matter… but especially this trial.

Some interesting information on the cinnarizine component, from the Meniere’s Society UK:

Cinnarizine has two pharmacological actions. It is a calcium antagonist, though not a powerful one. This acts mainly on the blood vessels and prevents constriction on these vessels. In theory it therefore improves the micro circulation of the ear. At the same time it has a mild antihistaminic effect.

Remember to subscribe to the email newsletter for updates related to this cinnarizine/bitter almond combination therapy (and news about other experimental tinnitus treatments in development).

References