Tryptophan Depletion in PD Patients Treated With STN DBS

Maastricht University Medical Centre (MUMC)

Status: Terminated

Conditions: Parkinson's Disease

Treatments: Device: Stimulator OFF; Device: Stimulator ON; Dietary Supplement: Tryptophan (TRP) depletion; Dietary Supplement: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT02632279

Tryptophan depletion in PD

Details and patient eligibility

About

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.

Full 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.

Enrollment: 7 patients

Sex: All

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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7 participants in 2 patient groups, including a placebo group

TRP depleted

Experimental group

Description:

TRP depleted protein drink

Treatment:

Dietary Supplement: Tryptophan (TRP) depletion

Device: Stimulator OFF

Device: Stimulator ON

Placebo

Placebo Comparator group

Description:

Balanced protein drink (+1.21g of TRP)

Treatment:

Device: Stimulator OFF

Device: Stimulator ON

Dietary Supplement: Placebo