Clinical trial NCT02632279: Tryptophan Depletion in PD Patients Treated With STN DBS
Official title: Tryptophan Depletion in Parkinson's Disease Patients Treated With Deep Brain Stimulation of the Subthalamic Nucleus: Effects on Mood and Motor Functions
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Parkinson's Disease
Keywords: Parkinson's disease
Deep Brain Stimulation
Subthalamic nucleus
Tryptophan depletion
Serotonin
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
Collaborators: name: Netherlands Brain Foundation
First posted: 2015-12-16
Enrollment: 7
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the effect of tryptophan depletion on mood and behavior in Parkinson's disease (PD) patients treated with deep brain stimulation (DBS) of the subthalamic nucleus (STN). By doing this, the investigators hope to be able to identify risk factors for and mechanisms underlying psychiatric side effects of STN DBS. The study will be an intervention study with a placebo controlled, randomized cross-over design.

Detailed description: Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor symptoms such as tremor, rigidity and slowness of movement. In later stages of the disease, when pharmacological treatment becomes less efficient, deep brain stimulation (DBS) of the subthalamic nucleus (STN) becomes a treatment option. Although motor symptoms improve significantly by DBS, a number of operated patients experience severe side effects, mostly related to mood, cognition or behavior. These adverse effects are most likely mediated through the serotonin (5-HT) system. Additionally, a dysfunction of the 5-HT system is implied in the pathophysiology of PD. PD patients are therefore regarded as 'vulnerable' to experiencing mood, cognitive and emotional problems due to changes in 5-HT activity.

To elucidate whether STN DBS is indeed the trigger for psychiatric and cognitive problems to arise in the PD patient, the 5-HT levels in PD patients implanted with STN DBS will be manipulated. In order to do this, the investigators will make use of the tryptophan (TRP) depletion method, an established research paradigm. In TRP depletion, the brain is depleted of TRP, the precursor of 5-HT, which consequently leads to lowered 5-HT levels. In both the normal and 5-HT depleted condition, mood- and cognitive parameters of the PD patients both with the STN stimulation on (ON) and off (OFF) will be assessed.

The goal is to get more insight into the effects of STN DBS in PD patients with a 5-HT vulnerabililty and the effects on 5-HT related mood and cognitive behaviour. This way, possible risk factors for and mechanisms underlying psychiatric side effects of STN DBS can be identified. The study is an intervention study with a placebo controlled, randomized cross-over design.

Eligibility criteria: Inclusion Criteria:

* subjects must be mentally competent
* subjects must have undergone STN DBS surgery for PD symptomatology

Exclusion Criteria:

* head injury
* stroke
* currentl malignancy or infection
* neurological disorders other than PD
* psychoactive medication: specifically antidepressants and antipsychotics ( a stable dose of benzodiazepines will be allowed)
* clinically relevant cognitive decline, operationalized as a MMSE score \< 24
* current psychiatric syptomatology, operationalized as a Hamilton Depression scale score \> 16 or a score \>2 on one of the MDS-UPDRS section I, items 1-6

Primary outcomes:
measure: Mood
timeFrame: There will be 6 measurements spread over 2 testing days with a wash-out period of min. 1 weak. baseline measure, 3.5 hours after intake of the amino acid mixture, and 5.5 hours after intake of the amino acid mixture
Secondary outcomes:
measure: Motor scores
timeFrame: There will be 6 measurements spread over 2 testing days with a wash-out period of min. 1 weak. baseline measure, 3.5 hours after intake of the amino-acid mixture, and 5.5 hours after intake of the amino-acid mixture
measure: Impulsivity
timeFrame: There will be 6 measurements spread over 2 testing days with a wash-out period of min. 1 weak. baseline measure, 3.5 hours after intake of the amino-acid mixture, and 5.5 hours after intake of the amino-acid mixture
measure: Emotional Responsiveness
timeFrame: There will be 4 measurements spread over 2 testing days with a wash-out period of min. 1 weak. baseline measure, 3.5 hours after intake of the amino-acid mixture
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
state: Limburg
Study officials:
affiliation: Maastricht University Medical Center
name: Yasin Temel, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: