Clinical TrialMajor Depressive Disorder (MDD)KetaminePlaceboCompleted

Ketamine for the Treatment of Depression in Parkinson's Disease

Randomised, double-blind, placebo-controlled parallel trial (n=51 actual) testing repeated IV ketamine infusions (0.5 mg/kg, six 40-minute infusions) for depression in people with Parkinson's disease.

Target Enrollment
51 participants
Study Type
Phase II interventional
Design
Randomized, quadruple Blind

Detailed Description

Parallel-group, randomised, quadruple-blind RCT comparing six intravenous ketamine infusions (0.5 mg/kg over 40 minutes) with saline placebo in participants with Parkinson's disease and major depressive disorder. Primary outcome is reduction in depression severity.

A subset will undergo baseline and post-treatment PET (synaptic density) and fMRI (functional connectivity) to examine mechanistic effects and network reorganisation underlying ketamine's antidepressant effect in PD.

Study Protocol

Preparation

sessions

Dosing

6 sessions
40 min each

Integration

sessions

Study Arms & Interventions

Ketamine infusion

experimental

Six IV ketamine infusions (0.5 mg/kg over 40 minutes) with cardiac monitoring.

Interventions

  • Ketamine0.5 mg/kg
    via IV• six infusions• 6 doses total

    0.5 mg/kg per infusion, administered over 40 minutes; up to 60 mg total per infusion as capped in protocol.

Saline infusion

inactive

Six IV saline (placebo) infusions administered over 40 minutes with monitoring.

Interventions

  • Placebo
    via IV• six infusions• 6 doses total

    Saline IV over 40 minutes (placebo comparator).

Participants

Ages
40 – 80
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • 1. Male or female ages 40-80 years, inclusive
  • 2. Clinical diagnosis of Parkinson's disease, stage 1, 2 or 3 as determined by the Hoehn and Yahr Scale
  • 3. Meet criteria for major depressive disorder (MDD) as determined by the Mini-International Neuropsychiatric Interview (MINI), and at least 15 on the MADRS
  • 4. For women of reproductive potential, use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation, as well as a negative pregnancy test at screening.
  • 5. Abstinence from drugs of abuse, other than alcohol, cannabis, nicotine and caffeine for the duration of the study.
  • 6. Stated willingness to comply with all study procedures and availability for the duration of the study.
  • 7. Provision of signed and dated informed consent form.

Exclusion Criteria

  • Exclusion Criteria:
  • 1. Presence of Dementia and a Montreal Cognitive Assessment (MoCA) score of less than 18.
  • 2. A primary psychiatric disorder (as determined by the MINI) except for MDD
  • 3. Active suicidal ideation with intent
  • 4. History of substance dependence in the last 2 years
  • 5. Current substance use disorder, except tobacco use disorder
  • 6. Prior clinical psychiatric treatment with ketamine or prior recreational use of ketamine
  • 7. A history of or current significant medical (e.g. cardiovascular, renal), or neurological (e.g. cerebrovascular, seizure, traumatic brain injury) illness other than PD that is unstable and significantly increase their risk and/or might affect the study objectives, as determined by study physicians
  • 8. Uncontrolled hypertension, defined as average blood pressure greater than or equal to 140 mmHg or an average diastolic blood pressure greater than or equal to 90 mmHg among those patients who have hypertension.
  • 9. Orthostatic hypotension (OH) that presents with symptoms sustained longer than a few minutes (e.g., light-headedness, blurred vision, dizziness, weakness, fatigue) or with syncope. OH is defined by a decrease in systolic blood pressure of 20 mm Hg or a decrease in diastolic blood pressure of 10 mm Hg within 3 minutes of standing compared with blood pressure from the sitting position.
  • 10. Inability to provide written informed consent according to the Yale Human Investigation Committee (HIC) guidelines.
  • 11. Any condition or finding that in the judgement of the PI significantly increases risk or significantly reduces the likelihood of benefit from participation in the study.
  • For participation in the PET/fMRI only:
  • 12. Prior radiation exposure for research purposes such that participation in this study would place them over FDA limits for annual radiation exposure (5 rem per yr)
  • 13. Contraindications to MRI scanning.
  • 14. Presence of a bleeding disorder as determined by the PT/INR (Prothrombin time and international normalized ratio) test

Study Details

Locations

Yale New Haven Hospital — New Haven, Connecticut, United States

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