Safety and Efficacy of Liraglutide in Parkinson's Disease

NCT02953665 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: U1111-1173-0106
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test the efficacy and safety of liraglutide in the treatment of patients with idiopathic Parkinson's disease (PD).

Conditions

Parkinson Disease

Keywords

Parkinson's Disease, Liraglutide; Antidiabetic agents; GLP-1 agonists; Insulin resistance

Outcome Measures

Primary Outcomes (3)

• Change in Unified Parkinson's Disease Rating Scale (UPDRS Part III Motor Examination) During "OFF" Time From Baseline to the End of Double-Blind Maintenance Period

  The UPDRS Part III (motor symptoms sub-scale) Assessment consists of 17 items, measured on a 5-Point scale (0-Normal to 4-Severe), addressing speech, facial expression, tremor at rest, action tremor, rigidity, finger taps, hand movements, hand pronation and supination, leg agility, arising from chair, posture, gait, postural stability, and body bradykinesia. The participant's score is calculated as a sum of the scores of the 17 individual questions. This sum score ranges from 0 to 108. Higher scores denote greater disability. A participant has been considered "OFF" when he/she has been off L-dopa for greater than 12 hours. During "OFF" time, the participant will not report feeling the effects of their anti-Parkinson's medication. The participant recorded the exact time of L-dopa intake. Assessment was only conducted greater than 12 hours after dosing with the participant reportedly feeling "OFF."

  From Baseline (Week 0) to end of Maintenance Period (up to 54 weeks)

• Change in the Non-Motor Symptoms Scale (NMSS) Total Score From Baseline to the End of the Double-Blind Maintenance Period

  The NMSS is a 30-item rater-based scale to assess a wide range of non-motor symptoms in patients with Parkinson's disease. The NMSS measures severity and frequency of non-motor symptoms across nine dimensions (cardiovascular, sleep/fatigue, mood/apathy, perceptual problems/hallucinations, attention/memory, gastrointestinal, urinary, sexual function, and miscellaneous which includes pain, taste/smell, weight change, and excessive sweating). Higher scores indicate a higher burden of these symptoms on the patient. There are 30 items to be scored, and the item scores are calculated as the product of severity and frequency; the total score is obtained by summing the item scores. The NMSS total score ranges from 0 to 360 with a lower score indicating fewer symptoms; a negative change from baseline indicates improvement in symptoms.

  From Baseline (Week 0) to the End of Maintenance Period (up to Week 54)

• Change in the Mattis Dementia Rating Scale (DRS-2) From Baseline to the End of Double-Blind Maintenance Period

  The DRS-2 assesses individuals in five areas resulting in five sub-scale scores. These scores are used to determine the overall score and level of cognitive functioning ability. The five areas include: Attention - measured using eight items Construction - measured using six items Conceptualization - measured using six items Initiation/Preservation - measured using eleven items Memory - measured using five items Higher raw scores indicate better cognitive status, with scores ranging from 0 to 144. Normative data in healthy subjects range from 137 to 144.

  From Baseline (Week 0) to the end of Maintenance Period (up to 54 weeks)

Secondary Outcomes (3)

• Change in the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) Index From Baseline to the End of Maintenance Period

  From Baseline (Week 0) to end of Maintenance Period (up to 54 weeks)

• Change in the Unified Parkinson's Disease Rating Scale Total Score From Baseline to the End of Double-Blind Maintenance Period

  From Baseline (Week 0) to end of Maintenance Period (up to 54 weeks)

• Change in The Parkinson's Disease Questionnaire (PDQ-39) From Baseline to the End of Double-Blind Maintenance Period

  From Baseline (Week 0) to end of Maintenance Period (up to 54 weeks)

Study Arms (2)

Liraglutide

ACTIVE COMPARATOR

Liraglutide 6 mg/ml (Novo Nordisk A/S) will be self-administered subcutaneously once daily at a maximum dose of 1.8 mg after a 2 week titration schedule.

Drug: Liraglutide

Placebo

PLACEBO COMPARATOR

Placebo will be self-administered subcutaneously once daily according to the same schedule.

Drug: Placebo

Interventions

Liraglutide DRUG

Liraglutide 6 mg/ml once daily at a maximum dose of 1.8 mg

Also known as: Victoza, Saxenda

Liraglutide

Placebo DRUG

Placebo (for Liraglutide) 6 mg/ml once daily at a maximum dose of 1.8 mg

Placebo

Eligibility Criteria

• Age: 25 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of idiopathic PD according to the United Kingdom Parkinson's Disease Society Brain Bank (UKPDSBB) criteria for at least 2 years
• Responsive to levodopa or dopaminergic treatment
• Male or female between 25 and 85 years of age at time of enrollment
• Women of child-bearing potential (WOCBP) must agree to use a reliable method of contraception (e.g., oral contraceptive or long-term injectable or implantable hormonal contraceptive, double barrier methods (such as condom plus diaphragm, condom plus spermicide foam, condom plus sponge), or intra-uterine devices) throughout the duration of the trial period and must have a negative serum pregnancy test at screening
• Male patients with female partners who have child bearing potential must agree to use adequate contraception throughout the duration of the trial period
• Capacity to give informed consent
• Ability to self-administer, or to arrange a care partner to administer trial drug, to comply with trial protocol, and to attend necessary clinic visits off medication

You may not qualify if:

• Diagnosis or suspicion of other causes for Parkinsonism, including drug- or toxin-induced parkinsonism and other neurodegenerative conditions, including multiple system atrophy, progressive supranuclear palsy, Huntington's disease, Wilson's disease, or Alzheimer's disease
• Active treatment with anticholinergic medications (e.g., trihexyphenidyl, tricyclic antidepressants)
• Known abnormality on CT or MRI brain imaging considered to cause symptoms or signs of neurological dysfunction, or considered likely to compromise compliance with trial protocol
• Concurrent dementia defined by a score lower than 120 on the MADRS-2 and/or inability to complete scale per neuropsychologist discretion
• Concurrent severe depression defined by a score greater than 29 on the Beck Depression Inventory
• Prior intracerebral surgical intervention for PD, including deep brain stimulation, lesional surgery, growth factor administration, gene therapy, or cell transplant
• Already actively participating in a trial of a device, drug, or surgical treatment for PD, or trial participation within 30 days prior to the baseline visit
• Diagnosis of diabetes mellitus of any type, established historically or by:
• Fasting plasma glucose levels equal or above 126 mg/dl
• Hemoglobin A1c equal or above 6.5%
• Active treatment with oral antidiabetic medications
• History of severe cardiac disease (e.g., angina, myocardial infarction, or cardiac surgery) in the preceding year
• Significant systemic illness likely to result in deterioration of the patient's condition or, in the Investigator's opinion, affect the patient's safety during the study, including in particular:
• History of pancreatitis
• Personal or family history of medullary thyroid carcinoma

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead
• Cure Parkinson's: collaborator
• Novo Nordisk A/S: collaborator

Study Sites (1)

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Related Publications (1)

• Zhang L, Zhang L, Li Y, Li L, Melchiorsen JU, Rosenkilde M, Holscher C. The Novel Dual GLP-1/GIP Receptor Agonist DA-CH5 Is Superior to Single GLP-1 Receptor Agonists in the MPTP Model of Parkinson's Disease. J Parkinsons Dis. 2020;10(2):523-542. doi: 10.3233/JPD-191768.

  PMID: 31958096 DERIVED

MeSH Terms

Conditions

Parkinson Disease; Insulin Resistance

Interventions

Liraglutide

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Limitations and Caveats

A single-center trial may prevent broad generalization of the results, and reduced the variability in data collection. There was a lack of diversity; a vast majority of study subjects were Caucasian. We did not collect cerebrospinal fluid (CSF) data, which may limit data interpretation. The lack of a video-recorded MDS-UPDRS prevented an independent review of motor scores that could have ruled out observer bias as the explanation for the recorded placebo effect.

Results Point of Contact

• Title: Vicki Manoukian, Neurology Clinical Research Program Manager
• Organization: Cedars-Sinai

Vicki.Manoukian@cshs.org

310-423-5067

Study Officials

• Michele Tagliati, MD

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Movement Disorders

Study Record Dates

• First Submitted: October 21, 2016
• First Posted: November 3, 2016
• Study Start: April 3, 2017
• Primary Completion: August 3, 2022
• Study Completion: August 3, 2022
• Last Updated: March 7, 2024
• Results First Posted: March 7, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)