Feasibility Study Assessing the Effect of Carbidopa/Levodopa Ratio on Orthostatic Hypotension in Multiple System Atrophy - Parkinsonian Type and Parkinson Disease. (CARBIDOH)

Julien Bally

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Orthostatic Hypotension, Dysautonomic; Parkinson Disease; Multi-system Atrophy - Parkinsonian Type

Treatments: Drug: Administration of Carbidopa/levodopa

Study type: Interventional

Funder types: Other

Identifiers

NCT06831500

2024-02568

Details and patient eligibility

About

This study is aimed at patients with multi-system atrophy - parkinsonian type (P-MSA) or Parkinson's disease (PD) receiving dopaminergic drugs and suffering from orthostatic hypotension (OH).

OH is a drop in blood pressure when standing, which can lead to symptoms of dizziness, lightheadedness, a black veil in front of the eyes and, when severe, can lead to fainting. HO is one of the symptoms present in AMS-P and PD.

The standard treatment for parkinsonian symptoms of slowness and stiffness is the administration of antiparkinsonian drugs containing dopamine. These dopaminergic drugs always contain 1) levodopa (which is the precursor of dopamine) and 2) an enzyme inhibitor, which may be either benserazide (in the case of Madopar® and its generics) or carbidopa (in the case of Sinemet® or Stalevo® and their generics) and whose role is to potentiate the effect of levodopa.

It has long been known that dopaminergic drugs aggravate HO. Through various mechanisms, this worsening of HO is linked as much to levodopa as to the enzyme inhibitor with which it is combined. However, investigators do not know the respective effects of these two molecules on HO.

In this study, investigators examine how the ratio of Carbidopa to levodopa affects HO in the various assays of the dopaminergic drug under study.

Enrollment: 36 estimated patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Informed consent form signed.
2. Patient over 18 years and under 80 years of age.
3. Patient with Multiple System Atrophy- Parkinsonian type (MSA-P) (confirmed by diagnostic criteria for clinically established and clinically probable multiple system atrophy (11); OR Patient with Parkinson Disease (PD) (12) presenting OH symptoms (getting at least one point at the 3 questions - n° 14, 15 and 16 - of the SCOPA-AUT scale that address orthostatic hypotension symptoms).
4. Patient currently receiving Dopamine-Replacement Therapy (i.e. Levodopa combined with Carbidopa or Benserazide).

Exclusion criteria

1. Patient unable to stand an overnight (at least 12 hours) withdrawal of their immediate-release DRT (last extended-, delayed-, or controlled-release dosage must be taken minimum 24 hours prior to the test).
2. Patient with known congestive heart failure, grades C and D, NYHA III and IV.
3. Patient with dementia (i.e. major cognitive impairment) associated to MSA-P or PD,
4. Patient with mild cognitive impairment, and unable to provide or understand informed consent, i.e. who does not have full capacity for discernment.
5. Current participation to other clinical trials.
6. Pregnant or lactating woman or willing to become pregnant.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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36 participants in 3 patient groups

Ratio 1:10 i.e. 20 mg Carbidopa / 200 mg Levodopa

Active Comparator group

Description:

This Carbidopa / Levodopa IMP ratio will be administered as a single dose, orally, at visit 1 or 2 or 3 (random order).

Treatment:

Drug: Administration of Carbidopa/levodopa

Ratio 1:4 i.e. 50 mg Carbidopa / 200 mg Levodopa

Active Comparator group

Description:

This Carbidopa / Levodopa IMP ratio will be administered as a single dose, orally, at visit 1 or 2 or 3 (random order).

Treatment:

Drug: Administration of Carbidopa/levodopa

Ratio 1:2 i.e. 100 mg Carbidopa / 200 mg Levodopa

Experimental group

Description:

This Carbidopa / Levodopa IMP ratio will be administered as a single dose, orally, at visit 1 or 2 or 3 (random order).

Treatment:

Drug: Administration of Carbidopa/levodopa