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NCT02953665

Safety and Efficacy of Liraglutide in Parkinson's Disease

Completed Phase 2 Results posted Last updated 7 March 2024
What this trial tests

Phase 2 trial testing Liraglutide in Parkinson Disease in 63 participants. Completed in 3 August 2022.

Timeline
3 April 2017
Primary endpoint
3 August 2022
3 August 2022

Quick facts

Lead sponsorCedars-Sinai Medical Center
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment63
Start date3 April 2017
Primary completion3 August 2022
Estimated completion3 August 2022
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Cedars-Sinai Medical Center

Who can join

Adults 25 to 85, any sex, with Parkinson Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

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-

GroupValue95% CI
Full Analysis Set (Liraglutide-treated Subjects)-2.3± 9.4
Full Analysis Set (Placebo-treated Subjects)-5.0± 7.1
Change in the Non-Motor Symptoms Scale (NMSS) Total Score From Baseline to the End of the Double-Blind Maintenance Period Primary · From Baseline (Week 0) to the End of Maintenance Period (up to Week 54)

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

GroupValue95% CI
Full Analysis Set (Liraglutide-treated Subjects)-5.5± 25.3
Full Analysis Set (Placebo-treated Subjects)6.5± 21.3
Change in the Mattis Dementia Rating Scale (DRS-2) From Baseline to the End of Double-Blind Maintenance Period Primary · From Baseline (Week 0) to the end of Maintenance Period (up to 54 weeks)

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.

GroupValue95% CI
Full Analysis Set (Liraglutide-treated Subjects)1.4± 9.3
Full Analysis Set (Placebo-treated Subjects)-0.3± 9.1
Change in the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) Index From Baseline to the End of Maintenance Period Secondary · From Baseline (Week 0) to end of Maintenance Period (up to 54 weeks)

Peripheral insulin resistance was assessed using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) Index. The HOMA-IR tool is a validated, non-invasive tool to assess the relationship between glucose and insulin. A score less than 1 means indicates insulin-sensitivity (Optimal). Greater than 1.9 indicates early insulin resistance, and a score greater than 2.9 indicates significant insulin resistance. An increase in one's HOMA-IR score may indicate increased insulin resistance.

GroupValue95% CI
Full Analysis Set (Liraglutide-treated Subjects)0.1± 1.1
Full Analysis Set (Placebo-treated Subjects)0.3± 0.8
Change in the Unified Parkinson's Disease Rating Scale Total Score From Baseline to the End of Double-Blind Maintenance Period Secondary · From Baseline (Week 0) to end of Maintenance Period (up to 54 weeks)

Total UPDRS Score (Parts I, II, III, and IV; administered in the ON condition) Change from Baseline to End of Maintenance Period. UPDRS I evaluation of mentation, behavior, and mood UPDRS II self-evaluation of the activities of daily life (ADLs) including speech, swallowing, handwriting, dressing, hygiene, falling, salivating, turning in bed, walking, and cutting food UPDRS III clinician-scored monitored motor evaluation UPDRS IV evaluation of complications in therapy and motor fluctuations, including OFF time and dyskinesia The UPDRS I, II, III, and IV scores and subscores are calculated as

GroupValue95% CI
Full Analysis Set (Liraglutide-treated Subjects)-4.9± 12.7
Full Analysis Set (Placebo-treated Subjects)2.3± 10.4
Change in The Parkinson's Disease Questionnaire (PDQ-39) From Baseline to the End of Double-Blind Maintenance Period Secondary · From Baseline (Week 0) to end of Maintenance Period (up to 54 weeks)

The Parkinson's Disease Questionnaire (PDQ-39) is a 39-item patient-reported rating scale that measures Parkinson's disease-specific health related quality of life. It covers 8 areas: mobility, activities of daily living (ADL), emotional well-being, stigma, social support, cognition, communication and bodily discomfort. Lower scores indicate better health related quality of life. PDQ-39 total scores range from 0 to 800. The total score can be summarised into the PDQ-39 summary index score (range of scores 0 to 100). A mean change in the PDQ-39 summary index score of about 1.6 points relates

GroupValue95% CI
Full Analysis Set (Liraglutide-treated Subjects)-2.5± 9.9
Full Analysis Set (Placebo-treated Subjects)11.2± 14.0

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Event collection commenced upon signing of consent at Screening and occurred at Baseline Week 1, Week 2, Week 6, Week 14, Week 28, Week 38, Week 54, and at follow-up Week 58.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Liraglutide
Serious: 9/42 (21%)
Deaths: 0/42
Placebo
Serious: 2/21 (10%)
Deaths: 0/21

Serious adverse events (9 terms)

ReactionSystemLiraglutidePlacebo
Fall/Admission for FallInjury, poisoning and procedural complications
Urinary Tract Infection (UTI)/Admission for UTIRenal and urinary disorders
Dizziness/Admission for DizzinessNervous system disorders
Hospital Admission for Averted StrokeVascular disorders
Worsening Urinary RetentionRenal and urinary disorders
Hospital Admission for Acute Kidney InjuryRenal and urinary disorders
Prostate CancerRenal and urinary disorders
Squamous Cell Carcinoma of CervixReproductive system and breast disorders
Invasive Lobular CarcinomaReproductive system and breast disorders
Other adverse events (15 terms — click to expand)

ReactionSystemLiraglutidePlacebo
Loss of AppetiteMetabolism and nutrition disorders
NauseaGastrointestinal disorders
DyspepsiaGastrointestinal disorders
Injection Site ReactionGeneral disorders
Other PainNervous system disorders
DiarrheaGastrointestinal disorders
ConstipationGastrointestinal disorders
Back PainMusculoskeletal and connective tissue disorders
VomitingGastrointestinal disorders
Upper Respiratory Tract InfectionInfections and infestations
FatigueGeneral disorders
Sleep DisorderNervous system disorders
HeadacheNervous system disorders
Urinary Tract InfectionRenal and urinary disorders
Worsening Off TimeNervous system disorders

Most-reported serious reactions: Fall/Admission for Fall, Urinary Tract Infection (UTI)/Admission for UTI, Dizziness/Admission for Dizziness, Hospital Admission for Averted Stroke, Worsening Urinary Retention, Hospital Admission for Acute Kidney Injury, Prostate Cancer, Squamous Cell Carcinoma of Cervix.

Data from ClinicalTrials.gov NCT02953665 adverse events section.

Sponsor's own description

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).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Old Drugs as New Treatments for Neurodegenerative Diseases.
    Durães F, Pinto M, Sousa E. · · 2018 · cited 193× · PMID 29751602 · DOI 10.3390/ph11020044
  2. Glucagon-like peptide-1 (GLP-1) receptor agonists and neuroinflammation: Implications for neurodegenerative disease treatment.
    Kopp KO, Glotfelty EJ, Li Y, Greig NH. · · 2022 · cited 185× · PMID 36372278 · DOI 10.1016/j.phrs.2022.106550
  3. The neuroprotective effects of glucagon-like peptide 1 in Alzheimer's and Parkinson's disease: An in-depth review.
    Reich N, Hölscher C. · · 2022 · cited 142× · PMID 36117625 · DOI 10.3389/fnins.2022.970925
  4. Neuroinflammation represents a common theme amongst genetic and environmental risk factors for Alzheimer and Parkinson diseases.
    Boyd RJ, Avramopoulos D, Jantzie LL, McCallion AS. · · 2022 · cited 101× · PMID 36076238 · DOI 10.1186/s12974-022-02584-x
  5. Incretin and insulin signaling as novel therapeutic targets for Alzheimer's and Parkinson's disease.
    Nowell J, Blunt E, Edison P. · · 2023 · cited 96× · PMID 36258018 · DOI 10.1038/s41380-022-01792-4
  6. Protective properties of GLP-1 and associated peptide hormones in neurodegenerative disorders.
    Hölscher C. · · 2022 · cited 92× · PMID 33900631 · DOI 10.1111/bph.15508
  7. Anti-Inflammatory Effects of GLP-1 Receptor Activation in the Brain in Neurodegenerative Diseases.
    Diz-Chaves Y, Mastoor Z, Spuch C, González-Matías LC, et al · · 2022 · cited 89× · PMID 36076972 · DOI 10.3390/ijms23179583
  8. Novel targeted therapies for Parkinson's disease.
    Ntetsika T, Papathoma PE, Markaki I. · · 2021 · cited 78× · PMID 33632120 · DOI 10.1186/s10020-021-00279-2

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Other trials of Liraglutide

Trials testing the same drug.

Other recruiting trials for Parkinson Disease

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Other Cedars-Sinai Medical Center trials

Trials by the same sponsor.

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