Tryptophan Depletion in PD Patients Treated With STN DBS

Parkinson's Disease Clinical Trial

Official title:

Tryptophan Depletion in Parkinson's Disease Patients Treated With Deep Brain Stimulation of the Subthalamic Nucleus: Effects on Mood and Motor Functions

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02632279
• Other study ID #: Tryptophan depletion in PD
• Status: Terminated
• Phase: N/A
• Start date: November 2015
• Est. completion date: November 15, 2017

Study information

• Verified date: August 2018
• Source: Maastricht University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: November 15, 2017
• Est. primary completion date: November 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

Dietary Supplement:
• Tryptophan (TRP) depletion
TRP depletion will be accomplished by administering a TRP-low amino acid protein drink containing 100 g of gelatin powder. The protein mixture consists of 18 amino acids. According to Dutch law, TRP is considered a food supplement and is not registered as a medicine.
• Placebo
The placebo treatment will consist of an identical amino acid protein drink containing 100 g of gelatin powder to which 1.21g TRP is added.

Device:
• Stimulator ON
Participants will be tested while their stimulator is turned ON
• Stimulator OFF
Participans will be tested while their stimulator is turned OFF

Locations

Country	Name	City	State
Netherlands	Maastricht University Medical Center	Maastricht	Limburg

Sponsors (2)

Lead Sponsor	Collaborator
Maastricht University Medical Center	Netherlands Brain Foundation

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mood	as assessed through the Profile of Mood States	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	Motor scores	as assessed through the MDS-UPDRS	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	Impulsivity	as assessed through a reaction time task	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	Emotional Responsiveness	as assessed through the emotional responsiveness task	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