Polycystic Kidney, Autosomal Dominant
Conditions
Keywords
kidney disease, polycystic kidney disease, autosomal dominant kidney disease, kidney cysts, PKD
Brief summary
This study will test to see if metformin is safe and if it is tolerated compared to placebo in adult Autosomal Dominant Polycystic Kidney Disease (ADPKD) patients with beginning stages of chronic kidney disease. We will also measure its effect on progression of kidney disease as reflected in the kidney size and the kidney function, along with its effect on kidney pain and quality of life.
Detailed description
There is growing evidence that metformin, a drug widely used for the treatment of type 2 diabetes and polycystic ovary syndrome, may serve as a novel therapy for individuals in the early stages of Autosomal Dominant Polycystic Kidney Disease ADPKD by activating the metabolic sensor AMP-activated protein kinase (AMPK). AMPK is activated under conditions of metabolic and other cellular stresses. Through its actions on downstream mediators, AMPK activation during low energy states decreases cellular energy consumption while stimulating energy generating pathways. It has been shown that AMPK phosphorylates and inhibits cystic fibrosis transmembrane conductance regulator (CFTR), thus suppressing epithelial fluid and electrolyte secretion. Similarly, AMPK phosphorylates the tuberin protein, leading to indirect inhibition of the mTOR pathway. Thus, AMPK inhibits both CFTR and mTOR, suggesting that targeted activation of this kinase by metformin may provide a therapeutic benefit in ADPKD. It has been shown that metformin treatment of kidney epithelial cells leads to stimulation of AMPK and subsequent inhibition of both mTOR and CFTR activity. It has also been shown that metformin slows cystogenesis in animal models of PKD, supporting the potential of this drug in ADPKD treatment.
Interventions
DRUGMetformin
Monitoring of tolerability and symptoms.
OTHERPlacebo
Monitoring of tolerability and symptoms.
Sponsors
Tufts Medical Center
University of Maryland, Baltimore
University of Southern California
United States Department of Defense
Kyongtae Ty Bae, M.D., Ph.D.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
Subject has Autosomal Dominant Polycystic Kidney Disease; Subject is fluent in English
Exclusion criteria
Subject is not on active military duty; Subject is not currently participating in another clinical trial; Subject's current GFR is not \<50 cc/min/1.73m2; Subject does not have diabetes; Subject does not have a systemic disease other than hypertension and PKD; Subject does not have a solitary kidney; Subject does not have an allergy or intolerance to metformin; Subject is not pregnant or lactating or intending to become pregnant within the next three years; Subject does not have an unstable or unclipped cerebral aneurysm; Subject does not have active coronary artery disease; Subject does not have an MRI incompatible device/implant; Subject does not have severe claustrophobia; Subject has not had any solid organ transplant; Subject does not have a Vitamin B12 deficiency; Subject does not currently take any medications that interact with metformin, such as nifedipine, furosemide, cationic drugs (amiloride, ranitidine, triamterene digoxin, procainamide, quinidine, vancomycin, trimethoprim); Subject does not currently take nor has taken (within 2 weeks) the drug tolvaptan (Jynarque or Samsca)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Gastrointestinal Symptoms Rating Scale (GSRS) to 24 Months | Baseline, 2 weeks, 6 weeks, 1 month, 3 months and every 3 months thereafter to 24 months | GSRS is a widely used, validated 15-item questionnaire used to assess GI symptom burden (minimum, maximum: 1, 7, where higher mean score is worse outcome). Mean change to 24 months, estimated with a repeated measures analysis (baseline, 2 weeks, 6 weeks, 1 month, 3 months and every 3 months thereafter to 24 months) using a linear mixed model. |
| Drug Tolerability | Baseline, 2 weeks, 6 weeks, 1 month, 3 months and every 3 months thereafter to 24 months | Tolerability was based on the first visit a participant responded no to the following question Can you tolerate this dose of study drug the rest of your life?, which was asked at baseline, 2 weeks, 6 weeks, 1 month, 3 months and every 3 months thereafter to 24 months. |
| Rate of Serious Adverse Events (SAE) | 26 months | Serious adverse events (SAE) occurring from the time a participant signs the informed consent (at the screening visit) until the end of the study, meeting 1 or more of the criteria of: 1) Resulting in death, 2) Non-elective hospitalization, 3) Life threatening (if patient continued on study drug would result in death), 4) Harming or disabling persistently or permanently , 5) Exceeding the nature, severity or frequency of risk described in the protocol or 6) Resulting in congenital anomaly. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Back Pain Frequency Over the Past 3 Months Since Last Visit | Baseline, 1 month, 3 months and every 3 months thereafter to 24 months | Odds ratio (OR) per month of back pain Often, Usually, or Always (vs. Never, Rarely, Sometimes) estimated with a repeated measures analysis (baseline, 1 month, 3 months and every 3 months thereafter to 24 months) using a generalized linear mixed model. |
| Estimated Glomerular Filtration Rate (eGFR) | Baseline, 2 weeks, and 6 weeks, 1 month, 3 months and every 3 months thereafter to 24 months | Mean change to 24 months, estimated with a repeated measures analysis (baseline, 2 weeks, 6 weeks, 1 month, 3 months and every 3 months thereafter to 24 months) using a linear mixed model. |
| Total Kidney Cyst Volume From Magnetic Resonance Imaging | Baseline, 6 months, 12 months, 18 months, 24 months | Annual percent change of height adjusted and natural log transformed total kidney cyst volume \[ln(htTKCV)\] was estimated with a linear mixed model. |
| Liver Volume From Magnetic Resonance Imaging | Baseline, 6 months, 12 months, 18 months, 24 months | Annual percent change of height adjusted and natural log transformed liver volume \[ln(htLV)\] was estimated with a linear mixed model. |
| Total Kidney Volume From Magnetic Resonance Imaging | Baseline, 6 months, 12 months, 18 months, 24 months | Annual percent change of height adjusted and natural log transformed total kidney volume \[ln(htTKV)\] was estimated with a linear mixed model. |
| Frequency Abdominal Fullness Interfered With Ability to Perform Usual Physical Activity Over the Past 3 Months Since Last Visit. | Baseline, 1 month, 3 months and every 3 months thereafter to 24 months | Odds ratio (OR) per month of abdominal fullness interfered Often, Usually, or Always (vs. Never, Rarely, Sometimes) estimated with a repeated measures analysis (baseline, 1 month, 3 months and every 3 months thereafter to 24 months) using a generalized linear mixed model. |
| Interference of Pain With Sleep Over the Past 3 Months Since Last Visit | Baseline, 1 month, 3 months and every 3 months thereafter to 24 months | Odds ratio (OR) per month of pain interfered with sleep Quite a bit or Extremely (vs. Not at all, A little bit, Moderately) estimated with a repeated measures analysis (baseline, 1 month, 3 months and every 3 months thereafter to 24 months) using a generalized linear mixed model. |
| Interference of Pain With Strenuous Physical Activity Over the Past 3 Months Since Last Visit | Baseline, 1 month, 3 months and every 3 months thereafter to 24 months | Odds ratio (OR) per month of pain interfered with strenuous physical activity Quite a bit or Extremely (vs. Not at all, A little bit, Moderately) estimated with a repeated measures analysis (baseline, 1 month, 3 months and every 3 months thereafter to 24 months) using a generalized linear mixed model. |
| Liver Cyst Volume From Magnetic Resonance Imaging | Baseline, 6 months, 12 months, 18 months, 24 months | Annual percent change of height adjusted and natural log transformed liver cyst volume \[ln(htLCV)\] was estimated with a linear mixed model. |
| Quality of Life Physical Component | Baseline, 1 month, 3 months and every 3 months thereafter to 24 months | Short Form-36 Quality of Life Physical Component Summary (SF-36 PCS) ranges from 0 (worst possible outcome) to 100 (best possible outcome). Mean change to 24 months, estimated with a repeated measures analysis (baseline, 1 month, 3 months and every 3 months thereafter to 24 months) using a linear mixed model. |
| Quality of Life Mental Component | Baseline, 1 month, 3 months and every 3 months thereafter to 24 months | Short Form-36 Quality of Life Mental Component Summary (SF-36 MCS) ranges from 0 (worst possible outcome) to 100 (best possible outcome). Mean change to 24 months, estimated with a repeated measures analysis (baseline, 1 month, 3 months and every 3 months thereafter to 24 months) using a linear mixed model. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Metformin Participants will be started on 500 mg of metformin once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Metformin: Monitoring of tolerability and symptoms. | 49 |
| Placebo Participants will be started on 500 mg of placebo once daily, with the following scheduled dose titrations:
* Increase to 500mg twice daily at week 2
* Increase to 1000mg qAM, 500mg qPM at week 4
* Increase to 1000mg twice daily at week 6 for the duration of their participation (26 months).
* Increased titrations based on tolerability
Placebo: Monitoring of tolerability and symptoms. | 48 |
| Total | 97 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Began Tolvaptan | 1 | 1 |
| Overall Study | Study burden | 3 | 3 |
| Overall Study | Unable/unwilling to take study medication | 2 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Metformin | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 97 Participants | 49 Participants | 48 Participants |
| Age, Continuous | 41.9 years STANDARD_DEVIATION 10.2 | 41.8 years STANDARD_DEVIATION 10.4 | 42.1 years STANDARD_DEVIATION 10.1 |
| BMI | 26.8 kg/m^2 STANDARD_DEVIATION 5.2 | 27.0 kg/m^2 STANDARD_DEVIATION 5.9 | 26.6 kg/m^2 STANDARD_DEVIATION 4.5 |
| Diastolic BP | 75.7 mmHg STANDARD_DEVIATION 8.7 | 76.8 mmHg STANDARD_DEVIATION 8.9 | 74.6 mmHg STANDARD_DEVIATION 8.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 2 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 89 Participants | 47 Participants | 42 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Gastrointestinal Symptoms Rating Scale | 1.4 scores on a scale STANDARD_DEVIATION 0.4 | 1.4 scores on a scale STANDARD_DEVIATION 0.5 | 1.3 scores on a scale STANDARD_DEVIATION 0.4 |
| GFR | 86.0 (ml/min/1.73 m²) STANDARD_DEVIATION 19.7 | 86.1 (ml/min/1.73 m²) STANDARD_DEVIATION 20.6 | 85.9 (ml/min/1.73 m²) STANDARD_DEVIATION 19 |
| Glucose | 89.7 mg/dL STANDARD_DEVIATION 8.8 | 88.6 mg/dL STANDARD_DEVIATION 8.4 | 90.9 mg/dL STANDARD_DEVIATION 9.1 |
| HbA1c | 5.2 % of total hemoglobin STANDARD_DEVIATION 0.3 | 5.2 % of total hemoglobin STANDARD_DEVIATION 0.3 | 5.2 % of total hemoglobin STANDARD_DEVIATION 0.3 |
| Height-adjusted liver volume | 1,121.6 mL/m STANDARD_DEVIATION 390 | 1,224.1 mL/m STANDARD_DEVIATION 490.7 | 1,019.0 mL/m STANDARD_DEVIATION 212.6 |
| Height-adjusted total kidney volume | 688.4 mL/m STANDARD_DEVIATION 475.7 | 625.8 mL/m STANDARD_DEVIATION 386.5 | 750.9 mL/m STANDARD_DEVIATION 547.8 |
| Mayo Imaging Class Class 1A | 15 Participants | 9 Participants | 6 Participants |
| Mayo Imaging Class Class 1B | 28 Participants | 13 Participants | 15 Participants |
| Mayo Imaging Class Class 1C | 26 Participants | 14 Participants | 12 Participants |
| Mayo Imaging Class Class 1D | 12 Participants | 6 Participants | 6 Participants |
| Mayo Imaging Class Class 1E | 8 Participants | 4 Participants | 4 Participants |
| Mayo Imaging Class Class 2 | 7 Participants | 2 Participants | 5 Participants |
| Mayo Imaging Class N/A | 1 Participants | 1 Participants | 0 Participants |
| PKD genotype N/A | 4 Participants | 2 Participants | 2 Participants |
| PKD genotype No mutation detected | 6 Participants | 2 Participants | 4 Participants |
| PKD genotype Other | 5 Participants | 1 Participants | 4 Participants |
| PKD genotype PKD1 | 65 Participants | 37 Participants | 28 Participants |
| PKD genotype PKD2 | 17 Participants | 7 Participants | 10 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 92 Participants | 46 Participants | 46 Participants |
| Region of Enrollment United States | 97 participants | 49 participants | 48 participants |
| Serum Creatinine | 0.93 mg/dL STANDARD_DEVIATION 0.23 | 0.92 mg/dL STANDARD_DEVIATION 0.24 | 0.94 mg/dL STANDARD_DEVIATION 0.23 |
| Sex: Female, Male Female | 70 Participants | 38 Participants | 32 Participants |
| Sex: Female, Male Male | 27 Participants | 11 Participants | 16 Participants |
| Short Form-36, Mental Component Summary | 52.4 scores on a scale STANDARD_DEVIATION 8.5 | 51.7 scores on a scale STANDARD_DEVIATION 9 | 53.1 scores on a scale STANDARD_DEVIATION 7.9 |
| Short Form-36, Physical Component Summary | 52.7 scores on a scale STANDARD_DEVIATION 6.4 | 52.2 scores on a scale STANDARD_DEVIATION 6.5 | 53.2 scores on a scale STANDARD_DEVIATION 6.3 |
| Systolic BP | 123.1 mmHg STANDARD_DEVIATION 13 | 122.2 mmHg STANDARD_DEVIATION 13.1 | 124.1 mmHg STANDARD_DEVIATION 13 |
| Vitamin B12 | 538.4 pg/mL STANDARD_DEVIATION 288.8 | 580.7 pg/mL STANDARD_DEVIATION 350.8 | 495.3 pg/mL STANDARD_DEVIATION 202.3 |
| Weight | 78.4 kg STANDARD_DEVIATION 17 | 78.5 kg STANDARD_DEVIATION 16.9 | 78.2 kg STANDARD_DEVIATION 17.4 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 49 | 0 / 48 |
| other Total, other adverse events | 21 / 49 | 13 / 48 |
| serious Total, serious adverse events | 4 / 49 | 4 / 48 |
Outcome results
Primary
Change in the Gastrointestinal Symptoms Rating Scale (GSRS) to 24 Months
GSRS is a widely used, validated 15-item questionnaire used to assess GI symptom burden (minimum, maximum: 1, 7, where higher mean score is worse outcome). Mean change to 24 months, estimated with a repeated measures analysis (baseline, 2 weeks, 6 weeks, 1 month, 3 months and every 3 months thereafter to 24 months) using a linear mixed model.
Time frame: Baseline, 2 weeks, 6 weeks, 1 month, 3 months and every 3 months thereafter to 24 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Metformin | Change in the Gastrointestinal Symptoms Rating Scale (GSRS) to 24 Months | -0.04 score on a scale |
| Placebo | Change in the Gastrointestinal Symptoms Rating Scale (GSRS) to 24 Months | -0.11 score on a scale |
Comparison: Linear mixed model with random intercept was used to compare the change in GSRS score as a function of time, the interaction between time and study arm, and clinical site.p-value: 0.595% CI: [-0.13, 0.26]Mixed Models Analysis
Primary
Drug Tolerability
Tolerability was based on the first visit a participant responded no to the following question Can you tolerate this dose of study drug the rest of your life?, which was asked at baseline, 2 weeks, 6 weeks, 1 month, 3 months and every 3 months thereafter to 24 months.
Time frame: Baseline, 2 weeks, 6 weeks, 1 month, 3 months and every 3 months thereafter to 24 months
Population: Intention to treat analysis
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Metformin | Drug Tolerability | 21 Participants |
| Placebo | Drug Tolerability | 14 Participants |
Comparison: The Gray's test of homogeneity for competing risks was used to compare cumulative incidence of tolerating the drug between study arms.p-value: 0.12Gray's test
Primary
Rate of Serious Adverse Events (SAE)
Serious adverse events (SAE) occurring from the time a participant signs the informed consent (at the screening visit) until the end of the study, meeting 1 or more of the criteria of: 1) Resulting in death, 2) Non-elective hospitalization, 3) Life threatening (if patient continued on study drug would result in death), 4) Harming or disabling persistently or permanently , 5) Exceeding the nature, severity or frequency of risk described in the protocol or 6) Resulting in congenital anomaly.
Time frame: 26 months
Population: Participants who received and took metformin or placebo
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Metformin | Rate of Serious Adverse Events (SAE) | 4 Participants |
| Placebo | Rate of Serious Adverse Events (SAE) | 4 Participants |
Comparison: Cumulative incidence between study arms and logistic regression was used to assess the association between study arms.p-value: 0.98Regression, Logistic
Secondary
Back Pain Frequency Over the Past 3 Months Since Last Visit
Odds ratio (OR) per month of back pain Often, Usually, or Always (vs. Never, Rarely, Sometimes) estimated with a repeated measures analysis (baseline, 1 month, 3 months and every 3 months thereafter to 24 months) using a generalized linear mixed model.
Time frame: Baseline, 1 month, 3 months and every 3 months thereafter to 24 months
Population: Intention to treat analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Metformin | Back Pain Frequency Over the Past 3 Months Since Last Visit | 0.95 odds ratio |
| Placebo | Back Pain Frequency Over the Past 3 Months Since Last Visit | 0.92 odds ratio |
Comparison: Generalized linear mixed model (logit link) with random intercept and slope was used to compare back pain frequency as a function of time, the interaction between time and study arm, and clinical site.p-value: 0.44Mixed Models Analysis
Secondary
Estimated Glomerular Filtration Rate (eGFR)
Mean change to 24 months, estimated with a repeated measures analysis (baseline, 2 weeks, 6 weeks, 1 month, 3 months and every 3 months thereafter to 24 months) using a linear mixed model.
Time frame: Baseline, 2 weeks, and 6 weeks, 1 month, 3 months and every 3 months thereafter to 24 months
Population: Intention to treat analysis
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Metformin | Estimated Glomerular Filtration Rate (eGFR) | -3.41 ml/min/1.73m^2 |
| Placebo | Estimated Glomerular Filtration Rate (eGFR) | -6.14 ml/min/1.73m^2 |
Comparison: Linear mixed model with random intercept was used to compare the change in eGFR as a function of time, the interaction between time and study arm, and clinical site.p-value: 0.295% CI: [-1.4, 6.87]Mixed Models Analysis
Secondary
Frequency Abdominal Fullness Interfered With Ability to Perform Usual Physical Activity Over the Past 3 Months Since Last Visit.
Odds ratio (OR) per month of abdominal fullness interfered Often, Usually, or Always (vs. Never, Rarely, Sometimes) estimated with a repeated measures analysis (baseline, 1 month, 3 months and every 3 months thereafter to 24 months) using a generalized linear mixed model.
Time frame: Baseline, 1 month, 3 months and every 3 months thereafter to 24 months
Population: Intention to treat analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Metformin | Frequency Abdominal Fullness Interfered With Ability to Perform Usual Physical Activity Over the Past 3 Months Since Last Visit. | 1.00 odds ratio |
| Placebo | Frequency Abdominal Fullness Interfered With Ability to Perform Usual Physical Activity Over the Past 3 Months Since Last Visit. | 0.99 odds ratio |
Comparison: Generalized linear mixed model (logit link) with random intercept and slope was used to compare abdominal fullness interfered as a function of time, the interaction between time and study arm, and clinical site.p-value: 0.83Mixed Models Analysis
Secondary
Interference of Pain With Sleep Over the Past 3 Months Since Last Visit
Odds ratio (OR) per month of pain interfered with sleep Quite a bit or Extremely (vs. Not at all, A little bit, Moderately) estimated with a repeated measures analysis (baseline, 1 month, 3 months and every 3 months thereafter to 24 months) using a generalized linear mixed model.
Time frame: Baseline, 1 month, 3 months and every 3 months thereafter to 24 months
Population: Intention to treat analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Metformin | Interference of Pain With Sleep Over the Past 3 Months Since Last Visit | 1.00 odds ratio |
| Placebo | Interference of Pain With Sleep Over the Past 3 Months Since Last Visit | 0.97 odds ratio |
Comparison: Generalized linear mixed model (logit link) with random intercept and slope was used to compare interference of pain with sleep frequency as a function of time, the interaction between time and study arm, and clinical site.p-value: 0.72Mixed Models Analysis
Secondary
Interference of Pain With Strenuous Physical Activity Over the Past 3 Months Since Last Visit
Odds ratio (OR) per month of pain interfered with strenuous physical activity Quite a bit or Extremely (vs. Not at all, A little bit, Moderately) estimated with a repeated measures analysis (baseline, 1 month, 3 months and every 3 months thereafter to 24 months) using a generalized linear mixed model.
Time frame: Baseline, 1 month, 3 months and every 3 months thereafter to 24 months
Population: Intention to treat analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Metformin | Interference of Pain With Strenuous Physical Activity Over the Past 3 Months Since Last Visit | 0.99 odds ratio |
| Placebo | Interference of Pain With Strenuous Physical Activity Over the Past 3 Months Since Last Visit | 0.95 odds ratio |
Comparison: Generalized linear mixed model (logit link) with random intercept and slope was used to compare interference of pain with strenuous physical activity frequency as a function of time, the interaction between time and study arm, and clinical site.p-value: 0.28Mixed Models Analysis
Secondary
Liver Cyst Volume From Magnetic Resonance Imaging
Annual percent change of height adjusted and natural log transformed liver cyst volume \[ln(htLCV)\] was estimated with a linear mixed model.
Time frame: Baseline, 6 months, 12 months, 18 months, 24 months
Population: Intention to treat analysis
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Metformin | Liver Cyst Volume From Magnetic Resonance Imaging | 12.72 annual percent change |
| Placebo | Liver Cyst Volume From Magnetic Resonance Imaging | 10.94 annual percent change |
Comparison: Linear mixed model with random intercept and slope was used to compare the annual percent change of ln(htLCV) as a function of time, the interaction between time and study arm, and clinical site.p-value: 0.895% CI: [-10.05, 14.76]Mixed Models Analysis
Secondary
Liver Volume From Magnetic Resonance Imaging
Annual percent change of height adjusted and natural log transformed liver volume \[ln(htLV)\] was estimated with a linear mixed model.
Time frame: Baseline, 6 months, 12 months, 18 months, 24 months
Population: Intention to treat analysis
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Metformin | Liver Volume From Magnetic Resonance Imaging | 1.60 annual percent change |
| Placebo | Liver Volume From Magnetic Resonance Imaging | 1.21 annual percent change |
Comparison: Linear mixed model with random intercept and slope was used to compare the annual percent change of ln(htLV) as a function of time, the interaction between time and study arm, and clinical site.p-value: 0.7295% CI: [-1.78, 2.61]Mixed Models Analysis
Secondary
Quality of Life Mental Component
Short Form-36 Quality of Life Mental Component Summary (SF-36 MCS) ranges from 0 (worst possible outcome) to 100 (best possible outcome). Mean change to 24 months, estimated with a repeated measures analysis (baseline, 1 month, 3 months and every 3 months thereafter to 24 months) using a linear mixed model.
Time frame: Baseline, 1 month, 3 months and every 3 months thereafter to 24 months
Population: Intention to treat analysis
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Metformin | Quality of Life Mental Component | 1.01 score on a scale |
| Placebo | Quality of Life Mental Component | -0.11 score on a scale |
Comparison: Linear mixed model with random intercept was used to compare the change in SF-36 MCS as a function of time, the interaction between time and study arm, and clinical site.p-value: 0.4995% CI: [-2.02, 4.25]Mixed Models Analysis
Secondary
Quality of Life Physical Component
Short Form-36 Quality of Life Physical Component Summary (SF-36 PCS) ranges from 0 (worst possible outcome) to 100 (best possible outcome). Mean change to 24 months, estimated with a repeated measures analysis (baseline, 1 month, 3 months and every 3 months thereafter to 24 months) using a linear mixed model.
Time frame: Baseline, 1 month, 3 months and every 3 months thereafter to 24 months
Population: Intention to treat analysis
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Metformin | Quality of Life Physical Component | -0.11 score on a scale |
| Placebo | Quality of Life Physical Component | -0.51 score on a scale |
Comparison: Linear mixed model with random intercept was used to compare the change in SF-36 PCS as a function of time, the interaction between time and study arm, and clinical site.p-value: 0.7295% CI: [-1.81, 2.6]Mixed Models Analysis
Secondary
Total Kidney Cyst Volume From Magnetic Resonance Imaging
Annual percent change of height adjusted and natural log transformed total kidney cyst volume \[ln(htTKCV)\] was estimated with a linear mixed model.
Time frame: Baseline, 6 months, 12 months, 18 months, 24 months
Population: Intention to treat analysis
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Metformin | Total Kidney Cyst Volume From Magnetic Resonance Imaging | 9.37 annual percent change |
| Placebo | Total Kidney Cyst Volume From Magnetic Resonance Imaging | 5.36 annual percent change |
Comparison: Linear mixed model with random intercept and slope was used to compare the annual percent change of ln(htTKCV) as a function of time, the interaction between time and study arm, and clinical site.p-value: 0.3195% CI: [-3.48, 11.65]Mixed Models Analysis
Secondary
Total Kidney Volume From Magnetic Resonance Imaging
Annual percent change of height adjusted and natural log transformed total kidney volume \[ln(htTKV)\] was estimated with a linear mixed model.
Time frame: Baseline, 6 months, 12 months, 18 months, 24 months
Population: Intention to treat analysis
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Metformin | Total Kidney Volume From Magnetic Resonance Imaging | 3.87 annual percent change |
| Placebo | Total Kidney Volume From Magnetic Resonance Imaging | 2.16 annual percent change |
Comparison: Linear mixed model with random intercept and slope was used to compare the annual percent change of ln(htTKV) as a function of time, the interaction between time and study arm, and clinical site.p-value: 0.3895% CI: [-2.11, 5.62]Mixed Models Analysis