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AzTrials

Huntington DiseasePhase 3TEMETNCT04826692

TEsting METformin Against Cognitive Decline in HD

A Phase 3 study testing Metformin in people with Huntington Disease, run by Instituto de Investigacion Sanitaria La Fe at 9 sites in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Multicenter, randomized, double-blind, placebo-controlled, parallel group study to assess the efficacy and safety of metformin treatment at a dose of 1700 mg / day in adults with Huntington's disease. Read more about this study

Who is it for?
Ages 21 to 65 years
Conditions the study is for
Huntington Disease
What is being tested?
Metformin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
60 participants
Where
9 sitesSpain
Study dates
11 Apr 2022to 10 Jun 2025
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Symptomatic positive clinical diagnosis of Huntington disease.
  • Presence of 36 CAG repeats (or more) in the hunting gene based on centralized CAG analysis.
  • Men or women between 21-65 years of age, inclusive, with an onset of HD at 18 years of age or older.
  • Women of childbearing potential (women who are not postmenopausal children or who have not undergone surgical sterilization at times) will need to be using a contraceptive method for 30 days before beginning study treatment, and will have contact with at least two methods of birth control throughout the duration of the study and up to 30 days after taking the last dose of treatment.
  • A sum of > 4 points on the UHDRS-TMS scale and a diagnostic confidence level of 4.
  • Scale of independence ≥ 75%.
Show all 11Show fewer
  • Score on the UHDRS-TFC scale ≥ 8 at the screening visit.
  • They must be trained and willing to provide written informed consent prior to any procedure related to the study to be performed at the screening visit. Patients with a legal guardian must be determined according to local requirements.
  • They must be trained and will require taking oral medication and will need to be determined to comply with the specific study procedures.
  • They must be able to travel to the study center and, in the judgment of the investigator, demonstrate that it is probable that they can continue traveling during the study.
  • Availability and willingness of a caregiver, informant, or family member to provide information during study visits that evaluate PBA-s. It is recommended that the caregiver be someone who cares for the patient at least 2 to 3 times a week and at least 3 hours per occasion. The suitability of the caregiver must be judged by the investigator.

Who cannot join

  • The participant has taken metformin in the last three months before the start of the study.
  • The participant has diabetes of any kind.
  • The participant is pregnant or lactating.
  • The participant has a medical condition other than HD (metabolism, kidney function, liver function, heart problems, etc.), or any contraindication against metformin.
  • The participant has an uncontrolled psychiatric condition.
  • Participant is allergic to metformin or any of the other ingredients of this medicine.
Show all 13Show fewer
  • The participant has kidney problems [creatinine clearance <60 ml / min calculated using Cockcroft-Gault formula] or liver problems.
  • The participant is dehydrated, from prolonged or severe diarrhea, or has vomited several times.
  • The participant has a serious infection.
  • The participant has been treated for heart failure or has recently had a heart attack, has severe circulation problems, or is having difficulty breathing.
  • The participant drinks> 6 units / day of alcohol (alcoholism).
  • Participants diagnosed with oncological disease.
  • Participants with a suicidal propensity, with an affirmative answer in items 4 or 5 in the C-SSRS at the screening visit.

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

Spain9 sites

  • Complejo Hospitalario de Albacete

    Albacete, Castille-La Mancha, 02006

  • Hospital General Universitario Dr. Balmis

    Alicante, Alicante, 03010

  • Hospital Universitario Mare de Déu de la Mercé

    Barcelona, Barcelona, 08035

  • Hospital Universitario Burgos

    Burgos, Castille and León, 09006

  • Hospital General Universitario de Elche

    Elche, Alicante, 03203

  • Hospital Universitario Ramón y Cajal

    Madrid, Madrid, 28034

  • Hospital Universitario Central de Asturias

    Oviedo, Principality of Asturias, 33011

  • Hospital Universitari Son Espases

    Palma de Mallorca, Balearic Islands, 07120

  • Hospital Universitario y Politécnico La Fe

    Valencia, València, 46026

Other trials in Spain

About this study

Official title: "Randomized, Double-blind, Placebo-controlled Study to Assess the Effect of Metformin, an Activator of AMPK, on Cognitive Measures of Progression in Huntington's Disease Patients"

Multicenter, randomized, double-blind, placebo-controlled, parallel group study to assess the efficacy and safety of metformin treatment at a dose of 1700 mg / day in adults with Huntington's disease.

The study consists of a screening period (2 to 4 weeks), followed by a 52-week double-blind treatment period and a follow-up visit (one month after the end of treatment).

Read the detailed description

Multicenter, randomized, double-blind, placebo-controlled, parallel group study to assess the efficacy and safety of treatment with metformin at a dose of 1700 mg / day in adults with HD.

A total recruitment of 60 patients is expected, which will be randomized in a 1: 1 ratio. 30 patients will receive metformin 1700 g / day, or placebo, for 52 weeks.

Patients will begin taking low doses of metformin, to facilitate tolerance and decrease intestinal discomfort. Half the daily dose (425 mg twice daily) will be administered over four weeks, along with the main meals. Patients who tolerate this dose well will continue with treatment by taking 850mg twice daily. Patients who don´t tolerate the initial dose (425 mg twice daily) will be withdrawn from the study.

Being tested
Metformin, Placebo
Keywords
Huntington disease, Metformin, AMPK, Huntingtina
Medical subject headings
Huntington Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MetforminDrug

    Also called Biguanides (oral antidiabetic)

    Metformin oral: 425 mg twice daily (initial dose) and 850 twice daily (maximum dose)

  • PlaceboDrug

    Also called Not appicable

    425 mg twice daily (initial dose) and 850 twice daily (maximum dose)

Study groups in NCT04826692
Study groupRoleWhat they receive
MetforminExperimentalTherapeutic group: Biguanidines (antidiabetic) Administration way: Oral Initial dose: 425 mg twice daily Maximum dose: 850 mg, twice daily Treatment duration: 12 months
Receives: Drug: Metformin
PlaceboPlacebo comparatorTherapeutic group: NA Administration way: Oral Initial dose: 425 mg twice daily Maximum dose: 850 mg, twice daily Treatment duration: 12 months
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Evaluate the effect of metformin on the scores obtained in different cognitive subtests that make up the Unified Huntington's Disease Rating Scale

    The tests that make up this subscale are the Symbol Digit Modalities Test.

    It is a comparative test that is collected throughout the entire trial to assess the progression of cognitive functions in patients.

    The test has 90 seconds time limit.

    Measured: Baseline - Week 52

  2. Evaluate the effect of metformin on the scores obtained in different cognitive subtests that make up the Unified Huntington's Disease Rating Scale (UHDRS).

    The tests that make up this subscale are the verbal fluency under phonetic slogan with the letters F, A and S,

    It is a comparative test that is collected throughout the entire trial to assess the progression of cognitive functions in patients.

    It consists of four categories of time 0-15; 16-30; 31-45 and 46-60 seconds and both hits and errors are counted.

    Measured: Baseline - Week 52

  3. Evaluate the effect of metformin on the scores obtained in different cognitive subtests that make up the Unified Huntington's Disease Rating Scale (UHDRS).

    The tests that make up this subscale are words and interference in the Stroop test.

    The Stroop test was performed to determine selective attention and inhibitory response (selective response to stimuli) to recognize a different stimulus among others. The test involves three kinds of stimuli: three columns of color names printed in black (condition A), three columns with different colors (red, green, blue or black) (condition B), and three columns of color names printed in a color that does not necessarily correspond to the word (for For example, the word "green" printed in blue, (condition C). The 3 parts of the test consist of A. speed of reading the words (names of colors printed in black), B. speed of nomination, the subject must name the colors. C. inhibitory response, called the interference test, where the subject must name the color in which the word with the name of the other color.

    The test has 45 seconds time limit.

    Measured: Baseline - Week 52

Secondary outcomes (7)

  1. Evaluate the effect of metformin on motor function in patients with Huntington's disease using the Unified Huntington's Disease Scale Total Motor Score.

    The motor function evaluation will include the following exams:

    Ocular Pursuit (horizontal and vertical), Saccade Initiation (horizontal and vertical), Saccade Velocity (horizontal and vertical), Dystrary, Lingual Protusion, Distonia (trunk and limbs), Korea (face , Mouth, trunk and extremities), Repulsion Test, Finger Tast (right and left), Pronate/ Supinate-Hands (right and left), Luria (palm test), Arm rigidity (right and left), Brady Kinesia-Body, Gait (walking difficulties), Tandem Walking.

    The initial stage of Huntington's Disease is related to a score greater than 4 on the Unified Huntington's Disease Rating Scale Total Motor Score (UHDRS-TMS) and a total functional capacity (UHDRS-TFC) greater than 8.

    Measured: Baseline - Visit 1 (Week 0) - Week 26 - Week 52

  2. Evaluate the effect of metformin on functional capacity in patients with Huntington´s disease using Unified Huntington's Disease Scale Functional Capacity.

    It is evaluated by means of a questionnaire on the following variables:

    Occupation, Finance, Daily life activities, Domestic Works Level of Care.

    The initial stage of Huntington's Disease is related to a score greater than 4 on the Unified Huntington's Disease Rating Scale Total Motor Score (UHDRS-TMS) and a total functional capacity (UHDRS-TFC) greater than 8.

    Where 0 its de worse situation and 3 its normal situation

    Measured: Baseline - Visit 1 (Week 0) - Week 26 - Week 52

  3. Evaluate the effect of metformin on behavioral signs and symptoms in patients with Huntington´s disease using Problem Behaviors Assessment-Short form (PBA-s)

    Specifically, will be evaluated on the changes in severity obtained in the items of depressed mood, suicidal ideation, anxiety, irritability, aggressiveness, apathy, persistent behavior and thinking, obsessive-compulsive behavior, delusional ideation, hallucinations, and disorientation.

    The severity is scored is the 0 (absent) to 4 (severe; almost unbearable for the caregiver) The frequency is scored is the 0 (never / almost never) to 4 (daily / almost daily most of the day)

    Measured: Baseline - Visit 1 (Week 0) - Week 26 - Week 52

  4. Evaluate if there are genetic markers associated to metformin by analysis pharmacogenetic.

    Analyze whether there are genetic markers associated with a better (or worse) response to metformin, through pharmacogenetics. The genotype of the patients will be analyzed on this material in a panel of single nucleotide polymorphisms (SNPs), related to the effect of Metformin and other medications that patients may be taking simultaneously.

    Measured: Visit 1 (week 0)

  5. Analyze the light chain protein of neurofilaments in peripheral blood.

    Analyze the light chain protein of neurofilaments in peripheral blood, as a circulating biomarker. Biomarker analysis will consist of obtaining information on the concentrations of various proteins, which tend to be released into the bloodstream when there are lesions in the nervous system.

    Measured: Visit 1 (week 0) and Visit 8 (Week 56)

  6. Evaluate the effect of metformin on the degree of independence in patients with Huntington's disease using the Unified Huntington's Disease Rating Scale Functional assessment and independence assessment.

    The scale consists in two parts. The first part is to make a functional evaluation with scored is 0 or 1. The second part evaluate degree of independence with scored the 5% to 100%.

    Measured: Baseline - Visit 1 (Week 0) - Week 26 - Week 52

  7. Evaluate the effect of metformin in patients body with Huntington's disease.

    Incidence of adverse events and incidence of abnormal laboratory test results,

    The classification of adverse events will be mild, moderate and serious by medical criteria.

    Measured: Baseline to Week 52

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Apr 2021
  2. Study start11 Apr 2022
  3. Primary completion10 Jun 2025
  4. Study completion10 Jun 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04826692
Sponsor's protocol ID
TEMET-HD
Acronym
TEMET
Status last verified
Jul 2025
First submitted
15 Sep 2020
Last updated
25 Sep 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Davies SW, Turmaine M, Cozens BA, DiFiglia M, Sharp AH, Ross CA, Scherzinger E, Wanker EE, Mangiarini L, Bates GP. Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell. 1997 Aug 8;90(3):537-48. doi: 10.1016/s0092-8674(00)80513-9.

    PubMed 9267033

  • Arrasate M, Mitra S, Schweitzer ES, Segal MR, Finkbeiner S. Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death. Nature. 2004 Oct 14;431(7010):805-10. doi: 10.1038/nature02998.

    PubMed 15483602

  • Mitra S, Tsvetkov AS, Finkbeiner S. Single neuron ubiquitin-proteasome dynamics accompanying inclusion body formation in huntington disease. J Biol Chem. 2009 Feb 13;284(7):4398-403. doi: 10.1074/jbc.M806269200. Epub 2008 Dec 10.

    PubMed 19074152

  • Slow EJ, Graham RK, Osmand AP, Devon RS, Lu G, Deng Y, Pearson J, Vaid K, Bissada N, Wetzel R, Leavitt BR, Hayden MR. Absence of behavioral abnormalities and neurodegeneration in vivo despite widespread neuronal huntingtin inclusions. Proc Natl Acad Sci U S A. 2005 Aug 9;102(32):11402-7. doi: 10.1073/pnas.0503634102. Epub 2005 Aug 2.

    PubMed 16076956

  • De Vos KJ, Grierson AJ, Ackerley S, Miller CC. Role of axonal transport in neurodegenerative diseases. Annu Rev Neurosci. 2008;31:151-73. doi: 10.1146/annurev.neuro.31.061307.090711.

    PubMed 18558852

  • Lee WC, Yoshihara M, Littleton JT. Cytoplasmic aggregates trap polyglutamine-containing proteins and block axonal transport in a Drosophila model of Huntington's disease. Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):3224-9. doi: 10.1073/pnas.0400243101. Epub 2004 Feb 20.

    PubMed 14978262

  • Ma TC, Buescher JL, Oatis B, Funk JA, Nash AJ, Carrier RL, Hoyt KR. Metformin therapy in a transgenic mouse model of Huntington's disease. Neurosci Lett. 2007 Jan 10;411(2):98-103. doi: 10.1016/j.neulet.2006.10.039. Epub 2006 Nov 15.

    PubMed 17110029

  • Vazquez-Manrique RP, Farina F, Cambon K, Dolores Sequedo M, Parker AJ, Millan JM, Weiss A, Deglon N, Neri C. AMPK activation protects from neuronal dysfunction and vulnerability across nematode, cellular and mouse models of Huntington's disease. Hum Mol Genet. 2016 Mar 15;25(6):1043-58. doi: 10.1093/hmg/ddv513. Epub 2015 Dec 17.

    PubMed 26681807

  • Sanz P, Rubio T, Garcia-Gimeno MA. AMPKbeta subunits: more than just a scaffold in the formation of AMPK complex. FEBS J. 2013 Aug;280(16):3723-33. doi: 10.1111/febs.12364. Epub 2013 Jun 24.

    PubMed 23721051

  • Porquet D, Casadesus G, Bayod S, Vicente A, Canudas AM, Vilaplana J, Pelegri C, Sanfeliu C, Camins A, Pallas M, del Valle J. Dietary resveratrol prevents Alzheimer's markers and increases life span in SAMP8. Age (Dordr). 2013 Oct;35(5):1851-65. doi: 10.1007/s11357-012-9489-4. Epub 2012 Nov 7.

    PubMed 23129026

  • Greer EL, Dowlatshahi D, Banko MR, Villen J, Hoang K, Blanchard D, Gygi SP, Brunet A. An AMPK-FOXO pathway mediates longevity induced by a novel method of dietary restriction in C. elegans. Curr Biol. 2007 Oct 9;17(19):1646-56. doi: 10.1016/j.cub.2007.08.047. Epub 2007 Sep 27.

    PubMed 17900900

  • Tourette C, Farina F, Vazquez-Manrique RP, Orfila AM, Voisin J, Hernandez S, Offner N, Parker JA, Menet S, Kim J, Lyu J, Choi SH, Cormier K, Edgerly CK, Bordiuk OL, Smith K, Louise A, Halford M, Stacker S, Vert JP, Ferrante RJ, Lu W, Neri C. The Wnt receptor Ryk reduces neuronal and cell survival capacity by repressing FOXO activity during the early phases of mutant huntingtin pathogenicity. PLoS Biol. 2014 Jun 24;12(6):e1001895. doi: 10.1371/journal.pbio.1001895. eCollection 2014 Jun.

    PubMed 24960609

  • Parker JA, Vazquez-Manrique RP, Tourette C, Farina F, Offner N, Mukhopadhyay A, Orfila AM, Darbois A, Menet S, Tissenbaum HA, Neri C. Integration of beta-catenin, sirtuin, and FOXO signaling protects from mutant huntingtin toxicity. J Neurosci. 2012 Sep 5;32(36):12630-40. doi: 10.1523/JNEUROSCI.0277-12.2012.

    PubMed 22956852

  • Parker JA, Arango M, Abderrahmane S, Lambert E, Tourette C, Catoire H, Neri C. Resveratrol rescues mutant polyglutamine cytotoxicity in nematode and mammalian neurons. Nat Genet. 2005 Apr;37(4):349-50. doi: 10.1038/ng1534. Epub 2005 Mar 27.

    PubMed 15793589

  • Shaw RJ. LKB1 and AMP-activated protein kinase control of mTOR signalling and growth. Acta Physiol (Oxf). 2009 May;196(1):65-80. doi: 10.1111/j.1748-1716.2009.01972.x. Epub 2009 Feb 19.

    PubMed 19245654

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Metformin in people with Huntington Disease, run by Instituto de Investigacion Sanitaria La Fe at 9 sites in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Evaluate the effect of metformin on the scores obtained in different cognitive subtests that make up the Unified Huntington's Disease Rating Scale (time frame: Baseline - Week 52). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04826692, which also lists 36 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2025; AzTrials last refreshed its copy on 29 Oct 2026.

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