Trial · NCT04220021
Safety and Therapeutic Potential of the FDA-approved Drug Metformin for C9orf72 ALS/FTD
NCT04220021, Phase 2, Active not recruiting, University of Florida; results first posted 2025-12-02
3 sourcestrials-2026-11-12-0.5.0
Cite this record
ConductScience Library. Safety and Therapeutic Potential of the FDA-approved Drug Metformin for C9orf72 ALS/FTD. Trials, record NCT04220021. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT04220021
On this page
Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- Safety and Therapeutic Potential of the FDA-approved Drug Metformin for C9orf72 ALS/FTD
- NCT number
- NCT04220021
- Status
- Active not recruiting
- Phases
- Phase 2
- Enrollment
- 41 participants, actual
- Lead sponsor
- University of Florida
- Conditions
- C9orf72 Amyotrophic Lateral Sclerosis (ALS), Frontotemporal Dementia
- Interventions
- Metformin
- First posted
- 2020-01-07
- Last updated
- 2026-08-20
- Results first posted
- 2025-12-02
- Limitations and caveats
Our C9orf72 ALS metformin clinical trial was not placebo-controlled but ALSFRS-R scores were compared to previously published C9orf72 ALS (PMID: 31578300) and all ALS patient (PMID: 25298304) natural history studies.
Source ClinicalTrials.gov
Registered outcomes3
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Number of Subjects With Unexpected Treatment-emergent Adverse Events [Safety and Tolerability] | 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 |
| Primary | Change in Repeat Associated Non-AUG (RAN) Protein Levels | Baseline through week 24. | Assessment of RAN protein levels in cerebrospinal fluid (CSF) samples from participants calculated as the percentage change in polyglycine-proline (GP) levels in ng/ml at study start \& end of the study as measured by Meso Scale Discovery (MSD) assays. |
| Secondary | Change in ALS Functional Rating Scale (ALSFRS-R) Score | Baseline through Week 24 | The Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) is a quickly administered (5 minute) ordinal rating scale (ratings 0-4) used to assess the capability and independence of subjects across 12 functional activities/questions. The score represents the sum of 12 functional domain items where each item is scored from 0 to 4 (Max score for each functional domain is 4 (Normal function); Minimum score for each functional domain = 0 (No ability to perform the task). The total score range is from 0 to 48, with a score of 48 meaning no functional impairment and 0 meaning complete loss of function across all domains. The mean values reported are at each study visit which occurred at baseline and at approximately 6, 12 and 24 weeks. The total number of days between study visits varied due to scheduling issues. |
Source ClinicalTrials.gov
Outcomes3
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Number of Subjects With Unexpected Treatment-emergent Adverse Events [Safety and Tolerability] | Baseline through 24 weeks | Forty-one subjects agreed to participate in the study. Twenty-three participants were defined as having Completed the study if they started the study medication and completed the ALSFRS-R evaluation at baseline and 24 weeks. | Participants | COUNT_OF_PARTICIPANTS |
| PRIMARY | Change in Repeat Associated Non-AUG (RAN) Protein Levels | Baseline through week 24. | Data from 17 of the 23 subjects were analyzed: 2 samples were excluded because the subjects were not drug compliant; data from 3 subjects were excluded because GP levels were not reliably detected; 1 sample was excluded because CSF was not able to be collected at the 24 week visit. | % change (ng/ml) from study start to end | MEDIAN |
| SECONDARY | Change in ALS Functional Rating Scale (ALSFRS-R) Score | Baseline through Week 24 | Twenty three subjects were analyzed as per protocol at baseline, week 6 and week 24. Twenty-two subjects were analyzed at week 12 because the ALSFRS-R was not completed due to coronavirus disease 2019 (COVID-19) travel difficulties at the 12 week time point. Two subjects who were not compliant with the medication throughout the study were excluded in Metformin compliant study completers study arm. | score on a scale | MEAN |
Source ClinicalTrials.gov
Results by group11
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Number of Subjects With Unexpected Treatment-emergent Adverse Events [Safety and Tolerability] | Study Completers | 0 | Participants | ||
| Number of Subjects With Unexpected Treatment-emergent Adverse Events [Safety and Tolerability] | All Participants | 0 | Participants | ||
| Change in Repeat Associated Non-AUG (RAN) Protein Levels | Study Completers With Reliable CSF MSD Values | -27.93 | Inter-Quartile Range -43.98 to -1.91 | % change (ng/ml) from study start to end | |
| Change in ALS Functional Rating Scale (ALSFRS-R) Score | Study Completers | Baseline | 38.61 | Standard Deviation 6.73 | score on a scale |
| Change in ALS Functional Rating Scale (ALSFRS-R) Score | Metformin Compliant Study Completers | Baseline | 38.57 | Standard Deviation 7.06 | score on a scale |
| Change in ALS Functional Rating Scale (ALSFRS-R) Score | Study Completers | Visit 2-approx. 6 wks | 37.74 | Standard Deviation 6.76 | score on a scale |
| Change in ALS Functional Rating Scale (ALSFRS-R) Score | Metformin Compliant Study Completers | Visit 2-approx. 6 wks | 37.57 | Standard Deviation 7.07 | score on a scale |
| Change in ALS Functional Rating Scale (ALSFRS-R) Score | Study Completers | Visit 3-approx. 12 wks | 36.30 | Standard Deviation 6.92 | score on a scale |
| Change in ALS Functional Rating Scale (ALSFRS-R) Score | Metformin Compliant Study Completers | Visit 3-approx. 12 wks | 36.33 | Standard Deviation 7.25 | score on a scale |
| Change in ALS Functional Rating Scale (ALSFRS-R) Score | Study Completers | Visit 4-approx.24 wks | 34.13 | Standard Deviation 8.35 | score on a scale |
1 to 10 of 11Source ClinicalTrials.gov
See all 11 results by groupParticipant flow3
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | Enrolled Subjects | 41 | |
| Overall Study | COMPLETED | Enrolled Subjects | 23 | |
| Overall Study | NOT COMPLETED | Enrolled Subjects | 18 |
Source ClinicalTrials.gov
Adverse events28
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Diarrhea | Gastrointestinal disorders | Enrolled Subjects | 16 | 41 | 21 |
| other | Diarrhea | Gastrointestinal disorders | Study Completers | 9 | 23 | 14 |
| other | Nausea | Gastrointestinal disorders | Enrolled Subjects | 6 | 41 | 6 |
| other | Nausea | Gastrointestinal disorders | Study Completers | 3 | 23 | 3 |
| other | Indigestion | Gastrointestinal disorders | Enrolled Subjects | 4 | 41 | 6 |
| other | Indigestion | Gastrointestinal disorders | Study Completers | 3 | 23 | 4 |
| other | Fall | Injury, poisoning and procedural complications | Enrolled Subjects | 10 | 41 | 20 |
| other | Fall | Injury, poisoning and procedural complications | Study Completers | 8 | 23 | 17 |
| other | Abrasion | Skin and subcutaneous tissue disorders | Enrolled Subjects | 4 | 41 | 8 |
| other | Abrasion | Skin and subcutaneous tissue disorders | Study Completers | 3 | 23 | 7 |
1 to 10 of 28Source ClinicalTrials.gov
See all 28 adverse eventsAdverse event totals6
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Enrolled Subjects | 0 | 41 |
| Total, all-cause mortality | Study Completers | 0 | 23 |
| Total, other adverse events | Enrolled Subjects | 35 | 41 |
| Total, other adverse events | Study Completers | 16 | 23 |
| Total, serious adverse events | Enrolled Subjects | 2 | 41 |
| Total, serious adverse events | Study Completers | 0 | 23 |
Source ClinicalTrials.gov
Papers7
The papers the trial lists on ClinicalTrials.gov.
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons3
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
| Comparison | Source |
|---|---|
| Enrolled Subjects vs Study Completers: deaths from any cause | Trial comparisons |
| Study Completers vs All Participants: Number of Subjects With Unexpected Treatment-emergent Adverse Events [Safety and Tolerability] | Trial comparisons |
| Enrolled Subjects vs Study Completers: serious adverse events | Trial comparisons |
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
For software
Read this trial from software.
The record and each of its lists are JSON, twenty rows a page. No key.
GET https://conductscience.org/api/trials/v1/NCT04220021
GET https://conductscience.org/api/trials/v1/NCT04220021/events?page=2