Safety and Therapeutic Potential of the FDA-approved Drug Metformin for C9orf72 ALS/FTD
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ClinicalTrials.gov Identifier: NCT04220021 |
Recruitment Status :
Active, not recruiting
First Posted : January 7, 2020
Last Update Posted : May 6, 2024
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
C9orf72 Amyotrophic Lateral Sclerosis (ALS) Frontotemporal Dementia | Drug: Metformin | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 18 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Intervention Model Description: | All participants receive medication |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Single-Center, Open Label Study to Assess the Safety and Tolerability of Metformin in Subjects With C9orf72 Amyotrophic Lateral Sclerosis Over 24 Weeks of Treatment |
Actual Study Start Date : | January 10, 2020 |
Estimated Primary Completion Date : | August 26, 2024 |
Estimated Study Completion Date : | August 26, 2024 |
Arm | Intervention/treatment |
---|---|
Experimental: C9orf72 positive ALS
Subjects with C9orf72 positive ALS will be instructed in the use of Metformin and receive the first dose of Metformin under supervision of the investigator during Visit 1, Day 2. Subjects will then continue on Metformin per the dose escalation schedule twice daily for 24 weeks. |
Drug: Metformin
Metformin is a widely used, well-tolerated drug that has been used for decades as a first-line defense for treating type 2 diabetes. Its safety has been well established. Subjects will begin treatment with Metformin at a dosage of 500mg with an escalation of dosage by 500mg every week to a maximal dosage of 2000mg. Dosing will be twice daily.
Other Name: Metformin hydrochloride sustained-release (SR) |
- Number of subjects with treatment-emergent adverse events [Safety and Tolerability] [ Time Frame: Baseline through 24 weeks ]The safety and tolerability of Metformin in participants with C9orf72 ALS currently treated with Metformin will be evaluated by the number of subjects with treatment-emergent adverse events
- Change in RAN protein levels [ Time Frame: baseline through week 24 ]Assess the RAN protein levels in cerebrospinal fluid (CSF) samples from participants at specific intervals.
- Change in ALS Functional Rating Scale (ALSFRS-R) score [ Time Frame: Baseline through Week 52 ]The ALSFRS-R is a quickly administered (5 minute) ordinal rating scale (ratings 0-4) used to determine subjects' assessment of their capability and independence in 12 functional activities/questions. Scores of 4 equaling 'normal' and scores of 0 equaling total lack of ability.
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Ages Eligible for Study: | 18 Years to 80 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Subjects have a diagnosis of probable or definite ALS in accordance with the Revisited El-Escorial Criteria.
- Subjects have a likely diagnosis of C9orf72 positive ALS/FTD.
- Subjects must be currently on an oral diet and able to take foods, pills and liquids by mouth equivalent to a score of 4 or above on the Functional Oral Intake Scale
- Subjects must have no known allergy to barium sulfate or Metformin.
- Subjects or subject's legally authorized representative must be willing and able to complete informed consent/assent and HIPAA authorization.
- Ability to comprehend and be informed of the nature of the study, as assessed by the PI or Co-Investigators.
- Subjects prescribed to take Metformin at or before the time of first dosing. (The study is open to subjects currently taking Metformin or subjects who have taken Metformin in the past).
- Availability to participate for the entire study duration.
- Female subjects of childbearing potential must have a negative urine pregnancy test prior to Videofluoroscopic Swallow Study (VFSS) exam during Visit 1, 3, and 4.
Exclusion Criteria:
- Subjects who score 3 or below on the Functional Oral Intake Scale
- Subjects who do not carry the C9ORF72 hexanucleotide repeat expansion as determined by laboratory analysis.
- Subjects with a history of clinically significant liver disease, renal disease, or any other medical condition judged to be exclusionary by the investigator.
- Subjects who are unwilling to sign informed consent or subjects who for any other reason in the judgment of investigator are unable to complete the study.
- Female subjects who have a positive urine pregnancy test (βhCG) at screening or visit 1, are trying to become pregnant or are breastfeeding.
- Subjects with active cancer within the previous 2 years, except treated basal cell carcinoma of the skin.
- Subjects who have taken any experimental drug within 30 days prior to enrollment or within 5 half-lives of the investigational drug -whichever is the longer period.
- Subjects with known history or presence of moderate or severe renal impairment as defined by an estimated glomerular filtration rate (eGFR) value below 30 mL/min/1.73 m2.
- Subjects with hepatic impairment as defined by baseline elevations of serum aminotransferases greater than 5 times upper limit of normal or evidence of liver dysfunction (e.g., elevated bilirubin).
- Use of potentially hepatotoxic drugs: (e.g., allopurinol, methyldopa, sulfasalazine).
- Subjects with clinically significant abnormal laboratory values in the judgment of the investigator.
- Subject with implanted electrical device (i.e. cardiac pacemaker or a neurostimulator), metal or metallic clip(s) in their body (i.e. an aneurysm clip in the brain) that will be damaged by participation in the MRI portion of the study.
- Anything else that, in the opinion of the investigator, would place the subject at increased risk or preclude the subject's full compliance with or completion of the study.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04220021
United States, Florida | |
UF Health at the University of Florida | |
Gainesville, Florida, United States, 32610 |
Principal Investigator: | Laura Ranum, PhD | University of Florida |
Responsible Party: | University of Florida |
ClinicalTrials.gov Identifier: | NCT04220021 |
Other Study ID Numbers: |
IRB201800620 UF2019-001 ( Other Identifier: University of Florida ) OCR20620 ( Other Identifier: UF OnCore ) UF2019-001 ( Other Identifier: UF Protocol ID ) |
First Posted: | January 7, 2020 Key Record Dates |
Last Update Posted: | May 6, 2024 |
Last Verified: | May 2024 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
ALS FTD Lou Gehrigs Disease |
Amyotrophic Lateral Sclerosis Metformin Motor Neuron Disease Frontotemporal Dementia Aphasia, Primary Progressive Pick Disease of the Brain Sclerosis Pathologic Processes Dementia Brain Diseases Central Nervous System Diseases Nervous System Diseases Neurocognitive Disorders Mental Disorders Neurodegenerative Diseases |
Neuromuscular Diseases Spinal Cord Diseases TDP-43 Proteinopathies Proteostasis Deficiencies Metabolic Diseases Frontotemporal Lobar Degeneration Aphasia Speech Disorders Language Disorders Communication Disorders Neurobehavioral Manifestations Neurologic Manifestations Hypoglycemic Agents Physiological Effects of Drugs |