Clinical trial NCT04826692: TEsting METformin Against Cognitive Decline in HD
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"
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Huntington Disease
Keywords: Huntington disease
Metformin
AMPK
Huntingtina
Lead sponsor: Instituto de Investigacion Sanitaria La Fe
Sponsor class: OTHER
First posted: 2021-04-01
Enrollment: 60
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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).

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 Patients who don´t tolerate the initial dose (425 mg twice daily) will be withdrawn from the study.

Eligibility criteria: Inclusion Criteria:

1. Symptomatic positive clinical diagnosis of Huntington disease.
2. Presence of 36 CAG repeats (or more) in the hunting gene based on centralized CAG analysis.
3. Men or women between 21-65 years of age, inclusive, with an onset of HD at 18 years of age or older.
4. 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.
5. A sum of \> 4 points on the UHDRS-TMS scale and a diagnostic confidence level of 4.
6. Scale of independence ≥ 75%.
7. Score on the UHDRS-TFC scale ≥ 8 at the screening visit.
8. 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.
9. They must be trained and will require taking oral medication and will need to be determined to comply with the specific study procedures.
10. 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.
11. 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.

Exclusion Criteria:

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

Primary outcomes:
measure: Evaluate the effect of metformin on the scores obtained in different cognitive subtests that make up the Unified Huntington's Disease Rating Scale
timeFrame: Baseline - Week 52
measure: Evaluate the effect of metformin on the scores obtained in different cognitive subtests that make up the Unified Huntington's Disease Rating Scale (UHDRS).
timeFrame: Baseline - Week 52
measure: Evaluate the effect of metformin on the scores obtained in different cognitive subtests that make up the Unified Huntington's Disease Rating Scale (UHDRS).
timeFrame: Baseline - Week 52
Secondary outcomes:
measure: Evaluate the effect of metformin on motor function in patients with Huntington's disease using the Unified Huntington's Disease Scale Total Motor Score.
timeFrame: Baseline - Visit 1 (Week 0) - Week 26 - Week 52
measure: Evaluate the effect of metformin on functional capacity in patients with Huntington´s disease using Unified Huntington's Disease Scale Functional Capacity.
timeFrame: Baseline - Visit 1 (Week 0) - Week 26 - Week 52
measure: Evaluate the effect of metformin on behavioral signs and symptoms in patients with Huntington´s disease using Problem Behaviors Assessment-Short form (PBA-s)
timeFrame: Baseline - Visit 1 (Week 0) - Week 26 - Week 52
measure: Evaluate if there are genetic markers associated to metformin by analysis pharmacogenetic.
timeFrame: Visit 1 (week 0)
measure: Analyze the light chain protein of neurofilaments in peripheral blood.
timeFrame: Visit 1 (week 0) and Visit 8 (Week 56)
measure: 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.
timeFrame: Baseline - Visit 1 (Week 0) - Week 26 - Week 52
measure: Evaluate the effect of metformin in patients body with Huntington's disease.
timeFrame: Baseline to Week 52
Other outcomes:
Locations:
city: Elche
country: Spain
facility: Hospital General Universitario de Elche
state: Alicante
city: Albacete
country: Spain
facility: Complejo Hospitalario de Albacete
state: Castilla La Mancha
city: Burgos
country: Spain
facility: Hospital Universitario Burgos
state: Castilla Y León
city: Palma De Mallorca
country: Spain
facility: Hospital Universitari Son Espases
state: Islas Baleares
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
state: Principado De Asturias
city: Valencia
country: Spain
facility: Hospital Universitario y Politécnico La Fe
state: València
city: Barcelona
country: Spain
facility: Unitat Polivalent Barcelona Nord
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
Study officials:
affiliation: Instituto de Investigación Sanitaria La Fe
name: Carmen Peiró, Phd, MD
role: STUDY_CHAIR
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