Not yet recruitingNAINTERVENTIONAL

Ketogenic Diet and Neuromodulation in Treatment Resistant Depression

This research is exploring a new way to help people with depression that hasn't gotten better with regular treatments. We're testing if a combination of a ketogenic diet (which changes how your body uses energy) and a type of brain stimulation called iTBS can relieve depressive symptoms more effectively than iTBS alone with a standard healthy diet. We also want to find out if it's practical for people to stick to the ketogenic diet during the treatment and if the diet actually changes their body's chemistry. Understanding if this combined approach is more helpful could open up new options for those struggling with difficult-to-treat depression.

At a glance

Status

Not yet recruiting

Phase

Sponsor

Sunnybrook Health Sciences Centre

Enrolment target

Start

01 Apr 2026

Estimated completion

01 Oct 2027

Major Depressive Disorder (MDD)Treatment Resistant Depression (TRD)

What is this study about?

This study is for adults who have major depression that hasn't improved much with at least two different antidepressant treatments. This type of depression is often called 'treatment-resistant depression'. We're trying to find out if combining two approaches might offer better results than one alone.

One part of the treatment is a special diet called the ketogenic diet. This diet involves eating very few carbohydrates (like sugars and starches) and more healthy fats. When you follow this diet, your body starts to burn fat for energy instead of sugar, producing substances called ketones. We want to see if this change in body chemistry, along with brain stimulation, can help improve mood.

The other part is a type of brain stimulation called accelerated intermittent theta burst stimulation (iTBS). This is a non-invasive treatment where magnets are used to stimulate specific areas of the brain that are involved in mood. Our main goal is to see if people who follow the ketogenic diet while getting iTBS treatment feel better than those who have iTBS with a regular healthy diet.

Key takeaways

Exploring if a special diet (ketogenic) plus brain stimulation helps severe depression.
Compares this combination to brain stimulation with a normal healthy diet.
Involves a 3-week diet lead-in, then brain stimulation.
Requires daily ketone checks and some hospital visits for tests.
Aims to find new ways to treat depression that hasn't responded to other things.

Who may be eligible?

This study is looking for volunteers between 18 and 65 years old, of any gender or background. To join, you need to be currently experiencing a major depressive episode and have moderate to severe symptoms. Most importantly, your depression must not have responded well to at least two standard antidepressant treatments. You also can't have had similar brain stimulation treatments (like rTMS or ECT) in the past.

There are several reasons why someone might not be able to join. For example, if you have certain medical conditions, a history of epilepsy, stroke, or severe neurological problems. You also can't be pregnant, breastfeeding, or planning to become pregnant during the study. If you've recently attempted suicide or have active thoughts of harming yourself, or if you have an active eating disorder, you wouldn't be able to participate for your safety and well-being.

Also, certain lifestyle factors or medications might mean you can't join. This includes if you already follow a ketogenic diet, have certain stomach or gut problems, or drink a lot of alcohol. Some specific medications, especially those for seizures or anxiety (except low doses of certain types), would also prevent you from joining. The study team will review all of this carefully to make sure it's safe and suitable for you.

Could this study suit you?

Answer these quick questions to see if you may be eligible. This is a guide only — the research team makes the final call.

Are you between 18 and 65 years old?
Has your depression not improved after trying at least two different antidepressant treatments?
Are you willing to try a specific diet plan for about 15 weeks?
Have you never had brain stimulation treatments like rTMS or ECT before?
Are you not pregnant, breastfeeding, or planning to be during the study?
Do you not have a history of serious neurological conditions or recent suicide attempts?

Answer every question to see your result.

What does participation involve?

If you decide to take part, you'll first be assigned to follow either a ketogenic diet or a standard healthy diet (based on common dietary guidelines), and you'll follow this diet for 3 weeks before the main treatment starts. During this time, and for the rest of the study, you'll need to measure your ketone levels daily with a simple finger-prick test.

After these 3 weeks, you'll begin a course of brain stimulation called iTBS while continuing your assigned diet. Throughout the study, you'll have regular check-ups with the study team. Before and after the iTBS treatment, you'll complete some questionnaires and assessments about your mood, give blood samples for health checks, and have MRI scans of your brain. The entire study, including the diet and treatment, will last for about 15 weeks.

Potential risks and benefits

Taking part in this study might help us learn more about new ways to treat depression, and you might personally find relief from your symptoms, though this is not guaranteed. However, there are potential risks, such as mild side effects from the ketogenic diet (like the 'keto flu' in the beginning) or from the iTBS treatment, which can include temporary headaches or discomfort at the stimulation site. There are also risks associated with blood tests and MRI scans, though these are generally small. You are free to withdraw from the study at any time, for any reason, without it affecting your usual medical care.

Locations (1)

Sunnybrook Health Sciences Centre
Verified postcode
Toronto, Canada

Common questions

What is a ketogenic diet?

It's a diet very low in sugar and starchy foods, high in healthy fats, which makes your body burn fat for energy.

What is iTBS?

It's a gentle, non-invasive brain stimulation treatment using magnetic pulses to help improve mood.

Will I have to eat only certain foods?

Yes, you'll follow a specific diet plan (either ketogenic or a standard healthy diet) provided by the study during the research.

How long does the study last?

The entire study and intervention period will be about 15 weeks.

Can I stop participating if I want to?

Yes, you can choose to leave the study at any time, and it won't affect your medical care.

How to find out more

Sean M Nestor, M.D., PhD

sean.nestor@utoronto.ca; sean.nestor@sunnybrook.ca 416-347-0257 Official trial record

Always speak to your GP or specialist before deciding to take part in a study.