Ketamine for Anorexia

(KETTLE Trial)

Overseen By Amanda E. Downey, MD

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Amanda Downey, MD

Must not be taking: Unsafe with ketamine

Disqualifiers: Psychotic disorder, Substance use, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 1 day

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a single site, single dose clinical trial of intravenous (IV) ketamine for medically hospitalized adolescents and young adults with anorexia nervosa or atypical anorexia nervosa. Eating disorder symptoms will be measured pre- and post-ketamine infusion. Investigators hypothesize that ketamine will increase cognitive flexibility, making medical hospitalizations less distressing by improving the ability to learn new, positive associations with food.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does mention that you cannot have any changes to psychiatric medications for a month before enrolling. Also, you cannot take medications that would be unsafe with ketamine.

What data supports the effectiveness of the drug ketamine for treating anorexia?

Some research suggests that ketamine, often used for depression, might help with anorexia. A case study showed a woman with chronic anorexia experienced complete recovery after using a ketogenic diet followed by ketamine infusions, and this remission lasted over 6 months. ^{1 2 3 4 5}

Is ketamine generally safe for human use?

Ketamine has been used safely in humans for anesthesia and depression treatment, with some studies noting temporary side effects like increased blood pressure and heart rate. In a study of 500 anesthesia cases, no major accidents were reported, suggesting it is generally safe when used appropriately. ^{6 7 8 9 10}

How does the drug Ketamine differ from other treatments for anorexia?

Ketamine is unique because it acts on the brain's NMDA receptors, which are involved in mood regulation, potentially offering rapid relief from symptoms like depression and anxiety that often accompany anorexia. This mechanism is different from traditional treatments that focus on nutritional rehabilitation and psychotherapy. ^{11 12 13 14 15}

Research Team

Amanda E. Downey, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for adolescents and young adults hospitalized with anorexia nervosa or atypical anorexia. Participants must be medically stable enough to receive a ketamine infusion. Specific inclusion and exclusion criteria details are not provided.

Inclusion Criteria

I haven't changed my psychiatric meds in the last month.

I agree to use effective birth control for two weeks after getting ketamine.

I have a healthcare provider managing my care.

Exclusion Criteria

Cardiac abnormalities identified on admission

Pregnancy as indicated by a positive urine pregnancy test during screening, lactation, or the intention of becoming pregnant within 3 months of entry into this trial

I am not on medications that interact badly with ketamine.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single dose of intravenous (IV) ketamine

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in eating disorder symptoms and cognitive flexibility

4 days

2 visits (in-person)

Treatment Details

Interventions

• Ketamine

Trial Overview The study tests if a single dose of IV ketamine can help patients with anorexia learn new, positive associations with food by increasing cognitive flexibility, potentially making hospital stays less stressful.

Participant Groups

Group I: Ketamine Infusion Experimental Treatment 1 Intervention

Ketamine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Ketalar for:

• Anesthesia
• Treatment-resistant depression

Approved in European Union as Ketalar for:

• Anesthesia
• Treatment-resistant depression

Approved in United States as Spravato for:

• Treatment-resistant depression

Approved in European Union as Spravato for:

• Treatment-resistant depression

Approved in Canada as Spravato for:

• Treatment-resistant depression

Who Is Running the Clinical Trial?

Amanda Downey, MD

Lead Sponsor

Trials

1

Recruited

20+

National Center for Advancing Translational Sciences (NCATS)

Collaborator

Trials

394

Recruited

404,000+

Findings from Research

In a study involving five participants with eating disorders and comorbid mood and anxiety disorders, weekly group-based ketamine-assisted psychotherapy (G-KAP) over 4 weeks led to significant improvements in depression and anxiety symptoms for most participants, with four showing notable reductions in depression scores and two in anxiety scores.

The ketamine treatment was well tolerated with no serious adverse events reported, indicating its safety and feasibility as an adjunct therapy in intensive residential eating disorder treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case series of group-based ketamine-assisted psychotherapy for patients in residential treatment for eating disorders with comorbid depression and anxiety disorders. Robison, R., Lafrance, A., Brendle, M., et al.[2022]

Oral ketamine is a potentially safe and effective treatment for depression, but it requires higher doses (2.0-2.5 mg/kg) compared to intravenous administration due to lower systemic absorption (20%-25%).

Despite its promise as a more accessible and affordable option for treatment, the current literature on oral ketamine is limited, and further research is needed to understand its pharmacokinetics, safety, and efficacy compared to other administration routes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Ketamine for Depression, 2: Practical Considerations. Andrade, C.[2020]

Subcutaneous (SC) administration of racemic ketamine and esketamine has shown rapid and robust antidepressant effects in both unipolar and bipolar patients, with response and remission rates ranging from 50% to 100% after single or multiple doses.

The studies indicated that SC ketamine is generally well-tolerated, with only transitory side effects, making it a promising and cost-effective treatment option for depression, especially in developing countries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous Ketamine in Depression: A Systematic Review. Cavenaghi, VB., da Costa, LP., Lacerda, ALT., et al.[2021]

An extended release oral ketamine tablet was found to be safe and well tolerated in a study of seven patients with treatment-resistant depression/anxiety, with no significant changes in vital signs and only one brief report of dissociation.

All patients experienced over 50% improvements in mood ratings over 96 hours, suggesting that while the onset of mood improvement is slightly delayed compared to injectable forms, this oral formulation could be a promising option for treating resistant depression and anxiety disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of extended release ketamine tablets in patients with treatment-resistant depression and anxiety: open label pilot study. Glue, P., Medlicott, NJ., Neehoff, S., et al.[2022]

Hypokinesia (restricted movement) in male Wistar rats led to significant increases in potassium (K+) losses and decreases in tissue K+ content, indicating that limited motor activity can negatively impact potassium levels in the body.

Supplementation with potassium chloride during hypokinesia resulted in even greater K+ losses and lower tissue K+ levels compared to unsupplemented rats, suggesting that higher potassium intake may paradoxically increase the risk of tissue depletion during periods of restricted activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potassium deposition during and after hypokinesia in potassium supplemented and unsupplemented rats. Zorbas, YG., Kakuris, KK., Charapakhin, KP., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

A case series of group-based ketamine-assisted psychotherapy for patients in residential treatment for eating disorders with comorbid depression and anxiety disorders. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Reply to Skokou, M. Comment on "Keeler et al. Ketamine as a Treatment for Anorexia Nervosa: A Narrative Review. Nutrients 2021, 13, 4158". [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Oral Ketamine for Depression, 2: Practical Considerations. [2020]

4. Germany pubmed.ncbi.nlm.nih.gov

Ketogenic diet and ketamine infusion treatment to target chronic persistent eating disorder psychopathology in anorexia nervosa: a pilot study. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Remission from Chronic Anorexia Nervosa With Ketogenic Diet and Ketamine: Case Report. [2022]

6. France pubmed.ncbi.nlm.nih.gov

[500 cases of general anesthesia without intubation with preservation of the pharyngolaryngeal reflexes]. [2013]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Subchronic ketamine alters behaviour, metabolic indices and brain morphology in adolescent rats: Involvement of oxidative stress, glutamate toxicity and caspase-3-mediated apoptosis. [2020]

8. Korea (South) pubmed.ncbi.nlm.nih.gov

Ketamine anaesthesia following premedication of rabbits with vitamin C. [2013]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Subcutaneous Ketamine in Depression: A Systematic Review. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of extended release ketamine tablets in patients with treatment-resistant depression and anxiety: open label pilot study. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Is glycyrrhizin sensitivity increased in anorexia nervosa and should licorice be avoided? Case report and review of the literature. [2013]

12. United States pubmed.ncbi.nlm.nih.gov

Potassium supplements' effect on potassium balance in athletes during prolonged hypokinetic and ambulatory conditions. [2013]

13. England pubmed.ncbi.nlm.nih.gov

A hypokalemic muscular weakness after licorice ingestion: a case report. [2021]

14. England pubmed.ncbi.nlm.nih.gov

Anorexia nervosa, liquorice and hypokalaemic myopathy. [2019]

15. Australia pubmed.ncbi.nlm.nih.gov

Potassium deposition during and after hypokinesia in potassium supplemented and unsupplemented rats. [2019]