Metabolic Cofactor Supplementation in Alzheimer's Disease (AD) and Parkinson's Disease (PD) Patients

NCT04044131 | Completed Phase 2

• 1 other identifier: Metabolic Cofactor Study
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 2

Brief Summary

This double-blind, randomized, placebo-controlled, investigator-initiated, multi-centre trial aims to establish metabolic improvements in AD and PD subjects by dietary supplementation with cofactors N-acetylcysteine, L-carnitine tartrate, nicotinamide riboside and serine. Concomitant use of pivotal metabolic cofactors via simultaneous dietary supplementation will stimulate to enhance hepatic β-oxidation and this study's hypothesis is that this will result in increased mitochondrial activity in human brain cell-types.

Conditions

Alzheimer Disease; Parkinson Disease

Outcome Measures

Primary Outcomes (4)

• Mini Mental State Examination (MMSE)

  The change in Mini Mental State Examination (MMSE) scores between the placebo and the treatment arms in AD patient from baseline to 4 weeks and 12 weeks. MMSE is global cognitive evaluation scale for AD patients. It consists of eleven questions and is evaluated over 30 points. It is normal between 24-30 points.

  4 weeks and 12 weeks

• Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog)

  The change in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) scores between the placebo and the treatment arms in AD patients from baseline to 4 weeks and 12 weeks. ADAS-cog is cognitive evaluation scale for AD patients. ADAS-Cog includes 11 tasks that include both subject-completed tests and observer-based assessments. Together these tasks assess the cognitive domains of memory, language, and praxis. The ADAS-cog is scored between 0-70 and high scores indicate poor status.

  4 weeks and 12 weeks

• Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)

  The change in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) scores between the placebo and the treatment arms in AD patients from baseline to 4 weeks and 12 weeks. ADCS-ADL is daily life activity evaluation scale for AD patients. This is a questionnaire structured to evaluate functional capacity in AD patients. It is scored between 0-78 and low scores indicate addiction. It is applied to the patient's relatives.

  4 weeks and 12 weeks

• Unified Parkinson's Disease Rating Scale (UPDRS)

  The change in Unified Parkinson's Disease Rating Scale (UPDRS) scores between the placebo and the treatment arms in PD patients from baseline to 4 weeks and 12 weeks. UPDRS is motor evaluation scale for PD patients. The UPDRS is used to follow the longitudinal course of Parkinson's disease. UPDRS has four parts: Part I (non-motor experiences of daily living), Part II (motor experiences of daily living, Part III (motor examination) and Part IV (motor complications). The first part 4, the second part 13, the third part 14 and the fourth part consists of 11 items. Each item scored between 0 (none) and 4 (heaviest). A score of 147 on the UPDRS scale represents the worst (total disability) with a score of zero representing (no disability).

  4 weeks and 12 weeks

Secondary Outcomes (19)

• Volumetric Magnetic resonance Imaging (MRI) and resting state functional magnetic resonance imaging (rest-fMRI)

  12 weeks

• Neuropsychiatric Inventory (NPI)

  4 weeks and 12 weeks

• Montreal Cognitive Assessment (MoCA)

  4 weeks and 12 weeks

• Changes in serum omic profile from baseline

  4 weeks and 12 weeks

• Microbiota analysis

  4 weeks and 12 weeks

Study Arms (2)

Treatment Arm

EXPERIMENTAL

Subjects in active treatment will receive dietary supplementation with N-acetylcysteine, L-carnitine tartrate, nicotinamide riboside, and serine, administered as a mixture.

Drug: Metabolic Cofactor Supplementation

Placebo Arm

PLACEBO COMPARATOR

Subjects will take a mixture of placebo as powder dissolved in water by mouth.

Drug: Sorbitol

Interventions

Metabolic Cofactor Supplementation DRUG

Dietary supplement consisting of serine, L-carnitine tartrate, N-acetylcysteine and nicotinamide riboside. Subjects in active treatment will receive dietary supplementation with N-acetylcysteine, L-carnitine tartrate, nicotinamide riboside, and serine, administered as a mixture. Half dosage of the co-factors will be given for two weeks (one dose taken just after dinner), and full dosage for 8 weeks (two equal doses taken just after breakfast and dinner).

Treatment Arm

Sorbitol DRUG

As placebo, sorbitol (5g) flavoured with strawberry aroma and colouring agent will be given.

Placebo Arm

Eligibility Criteria

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

You may qualify if:

• Men and women diagnosed with Parkinson's Disease (Hoehn Yahr 2-4, age \>18 years) or men and women diagnosed with Alzheimer's Disease. Include patients older than 50 years with mild to moderate Alzheimer's disease according to ADAS-cog (Alzheimer's Disease Assessment Scale-cognitive subscale; ADAS≥12) and the Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB; CDR≤2).
• Patients with stable treatments and clinical course

You may not qualify if:

• Inability or unwillingness to give written informed consent
• History of stroke, severe brain trauma, toxic drug exposure
• Neurological examination which indicate to Parkinson-Plus syndrome (i.e., pyramidal, cerebellar and autonomic dysfunction findings and gaze paralysis) for PD
• Uncontrolled Type 1 or type 2 diabetes
• Diarrhea (defined as more than 2 stool per day) within 7 days before enrolment
• Chronic kidney disease with an estimated glomerular filtration rate \<60 ml/min/1.73m2
• Significant cardiovascular co-morbidity (i.e. heart failure, documented coronary artery disease, valvular heart disease)
• Patients with active bronchial asthma
• Patients with phenylketonuria (contraindicated for NAC)
• Patients with histamine intolerance
• Clinically significant TSH level outside the normal range (0.04-6 mU/L)
• Known allergy for substances used in the study
• Concomitant medication use: Self-administration of dietary supplements such as any vitamins, omega-3 products, or plant stanol/sterol products within 1 month; Use of an antimicrobial agent in the 4 weeks preceding randomization
• Active smokers consuming \>10 cigarettes/day
• Alcohol consumption over 192 grams for men and 128 grams for women per week

Sponsors & Collaborators

• Istanbul Medipol University Hospital: lead
• ScandiBio Therapeutics AB: collaborator
• Alanya Alaaddin Keykubat University: collaborator
• Sahlgrenska University Hospital: collaborator
• KTH Royal Institute of Technology: collaborator

Study Sites (2)

Alanya Alaaddin Keykubat University Hospital

Antalya, 07400, Turkey (Türkiye)

Location

Medipol University Hospital

Istanbul, 34214, Turkey (Türkiye)

Location

Related Publications (2)

• Yulug B, Altay O, Li X, Hanoglu L, Cankaya S, Velioglu HA, Lam S, Yang H, Coskun E, Idil E, Bayraktaroglu Z, Nogaylar R, Ozsimsek A, Yildirim S, Bolat I, Kiliclioglu M, Bayram C, Yuksel N, Tozlu OO, Arif M, Shoaie S, Hacimuftuoglu A, Zhang C, Nielsen J, Turkez H, Boren J, Uhlen M, Mardinoglu A. Multi-omics characterization of improved cognitive functions in Parkinson's disease patients after the combined metabolic activator treatment: a randomized, double-blinded, placebo-controlled phase II trial. Brain Commun. 2025 Jan 6;7(1):fcae478. doi: 10.1093/braincomms/fcae478. eCollection 2025.

  PMID: 39816194 DERIVED

• Yulug B, Altay O, Li X, Hanoglu L, Cankaya S, Lam S, Velioglu HA, Yang H, Coskun E, Idil E, Nogaylar R, Ozsimsek A, Bayram C, Bolat I, Oner S, Tozlu OO, Arslan ME, Hacimuftuoglu A, Yildirim S, Arif M, Shoaie S, Zhang C, Nielsen J, Turkez H, Boren J, Uhlen M, Mardinoglu A. Combined metabolic activators improve cognitive functions in Alzheimer's disease patients: a randomised, double-blinded, placebo-controlled phase-II trial. Transl Neurodegener. 2023 Jan 26;12(1):4. doi: 10.1186/s40035-023-00336-2.

  PMID: 36703196 DERIVED

MeSH Terms

Conditions

Alzheimer Disease; Parkinson Disease

Interventions

Sorbitol

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies

Intervention Hierarchy (Ancestors)

Sugar Alcohols; Alcohols; Organic Chemicals; Carbohydrates

Study Officials

• Lutfu Hanoglu, MD, PhD

  Medipol University

  PRINCIPAL INVESTIGATOR

• Burak Yulug, MD, PhD

  Alanya Alaaddin Keykubat University

  PRINCIPAL INVESTIGATOR

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: Professor

Model Details: A total of 60 Alzheimer's and 60 Parkinson's disease patients will be randomized on a 2:1 basis to the cofactor mixture or placebo.

Study Record Dates

• First Submitted: July 17, 2019
• First Posted: August 5, 2019
• Study Start: December 2, 2019
• Primary Completion: March 15, 2021
• Study Completion: April 20, 2021
• Last Updated: August 8, 2022

Record last verified: 2022-08

Locations

TU (2)