Tryptophan Depletion in PD Patients Treated With STN DBS

NCT ID: NCT02632279

Last Updated: 2018-08-22

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-30
• Study Completion Date: 2017-11-15

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.

Conditions

Parkinson's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

TRP depleted

TRP depleted protein drink

Group Type: EXPERIMENTAL

Tryptophan (TRP) depletion

Intervention Type: DIETARY_SUPPLEMENT

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.

Stimulator ON

Intervention Type: DEVICE

Participants will be tested while their stimulator is turned ON

Stimulator OFF

Intervention Type: DEVICE

Participans will be tested while their stimulator is turned OFF

Placebo

Balanced protein drink (+1.21g of TRP)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DIETARY_SUPPLEMENT

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.

Stimulator ON

Intervention Type: DEVICE

Participants will be tested while their stimulator is turned ON

Stimulator OFF

Intervention Type: DEVICE

Participans will be tested while their stimulator is turned OFF

Interventions

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.

Intervention Type: DIETARY_SUPPLEMENT

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.

Intervention Type: DIETARY_SUPPLEMENT

Stimulator ON

Participants will be tested while their stimulator is turned ON

Intervention Type: DEVICE

Stimulator OFF

Participans will be tested while their stimulator is turned OFF

Intervention Type: DEVICE

Other Intervention Names

TRP depleted

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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Netherlands Brain Foundation

OTHER

Sponsor Role: collaborator

Maastricht University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yasin Temel, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Maastricht University Medical Center

Locations

Maastricht University Medical Center

Maastricht, Limburg, Netherlands

Countries

Netherlands

Other Identifiers

Tryptophan depletion in PD

Identifier Type: -

Identifier Source: org_study_id