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Active not recruitingPhase 2Results posted

Safety and Therapeutic Potential of the FDA-approved Drug Metformin for C9orf72 ALS/FTD

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

Lead sponsor

University of Florida

Asset

Metformin

Listed sites

Recruiting sites

Enrollment

actual

Study population

Frontotemporal dementia

Key I/E criterion

•Age 18-80

Primary endpoints

•Unexpected Treatment-emergent Adverse Events [Safety and Tolerability]•Repeat Associated Non-AUG (RAN) Protein Levels

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Other grantAGR DTD 12-20-2022ALS Association

Other grantCDMRP AL220089USAMRAA

Org study IDIRB201800620

NCT IDNCT04220021

Secondary IDOCR20620UF OnCore

Secondary IDUF2019-001UF Protocol ID

Timeline

Milestones

Study first posted2020-01-07actual

Study start2020-01-10actual

Primary completion2024-08-26actual

Last update posted2025-12-02actual

Results first posted2025-12-02actual

Study completion2026-06-30estimated

Assets

Drug assets

Metformin

Study populations

Who this study enrolls

Frontotemporal dementia

Eligibility

Who can enroll

Minimum age18 Years

Maximum age80 Years

SexAll

Healthy volunteersNot accepted

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 chromosome 9 open reading frame 72 (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.

Endpoints (6)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Function / daily living

Fluid / digital biomarkers

Safety / tolerability / PK

Function / daily living

2 endpoints

Secondary/protocol endpoint

Change in ALS Functional Rating Scale (ALSFRS-R) Score

Time frame:Baseline through Week 24

change from baseline, improvement

Secondary/registry result

Change in ALS Functional Rating Scale (ALSFRS-R) Score

Time frame:Baseline through Week 24

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard deviation
Study CompletersBaselinen=23 Participants	38.61	6.73
Visit 2-approx. 6 wksn=23 Participants	37.74	6.76
Visit 3-approx. 12 wksn=22 Participants	36.30	6.92
Visit 4-approx.24 wksn=23 Participants	34.13	8.35
Metformin Compliant Study CompletersBaselinen=21 Participants	38.57	7.06
Visit 2-approx. 6 wksn=21 Participants	37.57	7.07
Visit 3-approx. 12 wksn=20 Participants	36.33	7.25
Visit 4-approx.24 wksn=21 Participants	34.48	8.68

Fluid / digital biomarkers

2 endpoints

Primary/protocol endpoint

Change in Repeat Associated Non-AUG (RAN) Protein Levels

Time frame:Baseline through week 24.

percent change from baseline, improvement

Primary/registry result

Change in Repeat Associated Non-AUG (RAN) Protein Levels

Time frame:Baseline through week 24.

percent change from baseline, improvement

Posted result

Group	Value (median), % change (ng/ml) from study start to end	Reported bounds
Study Completers With Reliable CSF MSD Valuesn=17 Participants	-27.93	--43.98 - -1.91

p0.0245Sign test

Sign and binomial test with one-tail analysis where the null hypothesis predicts a 50/50 split (p=0.5) for two outcomes.

Safety / tolerability / PK

2 endpoints

Primary/protocol endpoint

Number of Subjects With Unexpected Treatment-emergent Adverse Events [Safety and Tolerability]

Time frame:Baseline through 24 weeks

event count, event

Primary/registry result

Number of Subjects With Unexpected Treatment-emergent Adverse Events [Safety and Tolerability]

Time frame:Baseline through 24 weeks

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Study Completersn=23 Participants	0	-
All Participantsn=41 Participants	0	-

Publications (7)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.